Dissertations / Theses: 'Adipogensi'

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AL, HAJ GHINA. "EFFECTS OF LIPID MIXTURE AND A SELECTIVE PPARG MODULATOR ON THE DIFFERENTIATION CAPABILITIES OF HUMAN DERIVED MESENCHYMAL STEM CELLS(HADSCS) DERIVED FROM HEALTHY AN D BREAST CANCER PATIENTS." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/784157.

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La sindrome metabolica è associata a molte complicanze che portano in particolare a malattie potenzialmente letali come l'obesità e il cancro. Per essere in grado di identificare soluzioni e trattamenti efficaci, dobbiamo indagare le cause alla base di questa sindrome. La nutrizione è un fattore importante da considerare nella prevenzione e nel trattamento della sindrome metabolica. La nutrizione ha effetto su quasi tutti i meccanismi del metabolismo del corpo umano, anche sull’adipogenesi Negli ultimi anni, è stato posto un enorme interesse sulo studio dell'adipogenesi in relazione soprattutto all'obesità. Diversi fattori influenzano l'adipogenesi primi fra tutti i nutrienti presenti nella dieta. Tra i nutrienti con effetto di contrasto all’obesità, i composti dietetici naturali godono di particolare interesse per aiutare a diminuire l'adiposità, quindi il rischio di sviluppare l'obesità e successivamente malattie correlate all'obesità come le malattie cardiovascolari e il diabete ma anche il cancro al seno. Per poter studiare questa correlazione in vitro, è possibile utilizzare un'ampia scelta di modelli cellulari. Le cellule mesenchimali isolate dal tessuto adiposo (hADSCs) sono una dei modelli sperimentali in vitro più usate per studiare l'adipogenesi superando i limiti che altri modelli cellulari hanno nella loro traslabilità all'uomo. In questo studio, lo scopo è stato di studiare l'adipogenesi utilizzando hADSCs anche in presenza di composti dietetici come lipidi e GMG-43AC un modulatore del recettore g (PPAR g) recettore gamma attivato dai proliferatori dei perossisomi. che ha mostrato un effetto positivo sull'inibizione dell'adipogenesi in cellule murine 3T3-L1. Inoltre, abbiamo indagato ulteriormente la sua applicazione su modelli di cellule umane per capire il suo meccanismo d’azione specifico che porta all’ inibizione di questo fenomeno. La parte sperimentale è stata impostata utilizzando la linea cellulare THP-1 differenziate a macrofagi in co-cultura con le hADSCs. Abbiamo notato che trattando le hADSCs con un cocktail di miscela lipidica, VI si verifica la diminuzione dell’espressione delle citochine pro-infiammatorie IL-6 e IL- 1b, valutata mediante real-time RT_PCR. Abbiamo anche notato un aumento dosedipendente dell’espressione di FABP-4. Inoltre, abbiamo anche dimostrato che le capacità differenziative di hADSCs isolate da tessuto adiposo peri-tumorale in casi di tumore della mammella, sono alterate. In questi casi le hADSCs hanno scarse capacità differenziative, valutate mediante saggi istologici ed espressione dell’mRNA di PPARγ e FABP-4. Al contrario, la presenza nel terreno di coltura delle hADSCs di una miscela lipidica (Composizione: acidi grassi non animali; 2 μg / ml arachidonico; 10 μg / ml di acido linoleico; 10 μg / ml di acido linolenico; 10 μg / ml di acido miristico;10 μg / ml di acido oleico; 10 μg / ml di acido palmitico; 10 μg / ml di acido stearico; 0,22 mg / ml di colesterolo dalla lana di pecora della Nuova Zelanda; 2,2 mg / ml di Tween-80; 70 μg / ml di tocoferolo acetato) ripristina l’espressione di PPARγ e l'accumulo di lipidi. In secondo luogo, GMG-43AC in entrambe le concentrazioni (0,5 mM e 2 mM) ha inibito l'accumulo di lipidi e ha mostrato una significativa diminuzione nell'espressione di geni specifici degli adipociti, come PPARγ, FABP-4 anche dopo la completa differenziazione di hADSC derivati da lipoaspirati . Ciò suggerisce che i composti dietetici sono fattori importanti nel differenziamento adipocitario e la dieta ha una grande influenza nella progressione e nella prevenzione di molte malattie metaboliche, tra cui l'obesità e il cancro.
Metabolic syndrome is associated with many complications especially leading to life threatening disorders such as obesity and cancer. To be able to identify solutions and natural treatments, we need to investigate the underlying causes of this syndrome. Nutrition is one important factor to consider in the prevention and treatment of the metabolic syndrome. Nutrition effects almost all metabolism mechanisms in the human body. One provident effect of nutrition is adiposity. Over the recent years, an interest was noted to studying adipogenesis in relation to obesity. Different factors affect adipogenesis including natural dietary compounds to help decrease adiposity, therefore the risk of developing obesity and later on obesity related diseases such as breast cancer. To be able to study this correlation in-vitro, a wide choice of cell models can be used. Human adipose derived mesenchymal cells (hADSCs) are one of the top choices used to study adipogenesis overcoming the limitations that other cell models have in their applicability to humans regarding the prevailing difference in their metabolism and physiology. In this study, the aim was to study adipogenesis using hADSCs in presence of dietary compounds such as lipids and GMG-43AC, a natural selective peroxisome proliferator-activated receptor g (PPAR g) modulator, that seems to have a positive effect on inhibiting adipogenesis in murine 3T3-L1 cells. We wanted to investigate further on its application on human cell models and try to understand its mechanism in inhibiting this phenomenon. The protocols were set up using the THP-1 cell line, which we noticed upon using a Lipid mixture cocktail (Composition: Non-animal fatty acids; 2 μg/ml arachidonic; 10 μg/ml linoleic acid; 10 μg/ml linolenic acid: 10 μg/ml myristic acid; 10 μg/ml oleic acid; 10 μg/ml palmitic acid; 10 μg/ml stearic acid; 0.22 mg/ml cholesterol from New Zealand sheep′s wool; 2.2 mg/ml Tween-80; 70 μg/ml tocopherol acetate), a decrease in pro-inflammatory cytokines IL-6 and IL-1b. We also noticed a doseIV dependent increase of FABP-4. Our findings regarding hADSCs, that PPARγ expression and lipid accumulation was restored upon the presence of lipid mixture in breast cancer hADSCs that were derived from breast tissue. Secondly, GMG-43AC in both concentrations (0.5mM and 2mM) inhibited lipid accumulation and showed a significant decrease in the expression of adipocyte-specific genes, such as PPARγ and FABP-4 even after the full differentiation of hADSCs that were derived from lipoaspirates. This suggests that dietary compounds are important factors in adipose differentiation and diet has a big influence in the progression and prevention in many metabolic diseases, such as obesity and cancer.

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Hafner, Anne-Laure. "Étude des progéniteurs adipeux dérivés des cellules souches pluripotentes induites humaines." Thesis, Nice, 2015. http://www.theses.fr/2015NICE4062.

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Chez les mammifères, on distingue principalement deux types de tissu adipeux (TA) : le TA blanc permet le stockage de l’énergie alors que le TA brun est spécialisé dans la thermogénèse induisant une dépense énergétique. Aujourd’hui, un troisième type d’adipocyte, nommé beige/ brite, est également reconnu. Ces cellules recrutées au sein du TA blanc, possèdent le même potentiel que les adipocytes bruns. L’identification des voies de signalisation permettant de réguler le développement des adipocytes blancs, beiges et bruns reste encore aujourd’hui à être déterminée. La génération des cellules souches pluripotentes induites (hiPS) a permis d’établir un nouveau modèle d’étude des étapes précoces de l’adipogénèse humaine. Nous avons démontré que la génération des progéniteurs adipeux (PA) blancs et bruns est régulée par la voie de l’acide rétinoïque pendant la différenciation in-vitro des cellules hiPS. La caractérisation moléculaire de ces deux types de PA a révélé l’implication du facteur Pax3 dans l’acquisition du phénotype brun. Au cours de cette étude, nous avons constaté que les PA dérivés de cellules hiPS (hiPSC-PA) présentaient un faible potentiel adipocytaire. Nous avons identifiés les facteurs permettant de différencier avec une forte efficacité les hiPSC-PA comprenant l’EGF, l’acide ascorbique, l’hydrocortisone et l’inhibiteur de la voie du TGFβ, le SB 431542. Lors d’expériences préliminaires, nous avons analysé l’effet de la surexpression du facteur HOXC8 sur la différenciation des PA. L’expression ectopique de ce facteur conduit à des réponses distinctes sur le phénotype et la différenciation des hiPSC-PA et ceux provenant de tissus adultes
In mammals, two types of adipose tissue coexist: the white (WAT) wich is involved in energy storage and the brown (BAT) which is specialized in energy expenditure. Beige adipocytes have recently been described as brown –like adipocytes and represent a third type of adipocytes that are recruited in WAT. The molecular mechanisms involved in the generation of these different types of adipocytes remains unknow in humans, mainly because of the lack of appropriate in vitro cellular models. The human induced Pluripotent Stem (hips) cells are a good model to study the earliest steps of human adipogenesis. We have shown that the generation of white and brown adipocytes progenitors (AP) is regulated by acid retinoic signaling pathway during hips cells differentiation. Functional experiments indicated that the transcription factor Pax3 is a molecular mediator of the brown phenotype. During this study, we could see that AP derived from hips cells display a low adipogenic capacity as compared to progenitors derived from adult adipose tissue. We show in this work that treatment with TGFβ pathway inhibitor SB431542 together with ascorbic acid, hydrocortisone and EGF promoted differentiation of non- genetically modified hiPSCs-BAPs at a high rate. During preliminary results, we have analyzed the role of the transcription factor Hoxc8 on PA differentiation. The surexpression of this factor lead to distinct answers on the phenotype and differentiation between hiPSCs-AP and adult-derived AP

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Yarmo, Michelle Nada. "The anti-adipogenic effect of macrophage-conditioned medium on on 3T3-L1 and human adipogenesis." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28322.

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Macrophages accumulate in the adipose tissue of obese rodents and humans. We and others have reported that macrophage-secreted factors inhibit adipogenesis. This study aims to investigate the molecular mechanisms underlying this inhibitory effect. Murine 3T3-L1 preadipocytes were differentiated with medium conditioned by murine J774 macrophages (J774-MacCM) or human THP-1 macrophages (THP-1-MacCM). Clonal expansion, an early required adipogenic event, was inhibited by both MacCMs Rb phosphorylation, required for cell cycle progression, was impaired by J774-MacCM. To expand our studies to a more physiological setting, human abdominal subcutaneous preadipocytes were differentiated with THP-1-MacCM or with conditioned medium from blood monocyte-derived macrophages (MDM-CM) activated with LPS. The IKKbeta/NF-kappabeta pathway appeared to be required for the THP-1 MacCM anti-adipogenic effect. Furthermore, human preadipocytes differentiated in MDM-CM (LPS) displayed a distinct morphology, altered fibronectin expression, as well as reduced lipid accumulation and expression of adipogenic markers. These studies suggest that macrophage-secreted factors impair proximal events in the adipogenic program.

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Carvalho, Polliane Morais de 1981. "Evaluation of masticatory, salivary and anthropometric function, presence of volatile sulphur compounds in young adults and changes in salivary gland pos adipogenesis induction in animal model = Avaliação da função mastigatória, salivar, antropométrica, presença de compostos sulfurados voláteis em adultos jovens e alterações em glândula salivar após indução de adipogênese em modelo animal." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/287939.

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Orientador: Maria Beatriz Duarte Gavião
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Este estudo investigou a função mastigatória, o paladar, a presença de compostos sulfurados voláteis (CSV) e a bioquímica salivar em sujeitos saudáveis (18-33 anos), e a indução de adipócitos em glândula salivar e suas implicações em modelo animal. Três estudos foram conduzidos, apresentados na forma de capítulos. Capítulo 1: Investigou a performance e habilidade mastigatória, paladar e a possível relação com gênero, índice de massa corporal (IMC), circunferência de cintura (CC) e fluxo salivar estimulado (Stim) e não estimulado (Unst). Foram avaliados 171 indivíduos, (125? 46?). A performance mastigatória foi determinada pela capacidade de fragmentação do Optocal plus e habilidade mastigatória com o uso da escala visual analógica (EVA). O paladar foi verificado pela percepção dos quatro sabores primários. A estatística descritiva, teste de normalidade, correlação, comparação e modelos de regressão foram utilizados, sendo as variáveis dependentes a função mastigatória e o paladar e as independentes: gênero, idade, variáveis antropométricas e fluxo salivar. Na análise de regressão linear múltipla, as variáveis independentes não predisseram o modelo para performance mastigatória. Com a habilidade mastigatória (HM) o modelo explicou 14% da variabilidade e para o paladar 5%. Os resultados indicaram que a performance não foi relacionada com parâmetros antropométricos e salivares em indivíduos jovens saudáveis. A habilidade foi relacionada com IMC, CC e gênero. O paladar foi fracamente relacionado ao IMC e CC. Capítulo 2: Verificou a bioquímica salivar e presença de CSV e a possível interferência do IMC, fluxo e pH stim/unst. Para a verificação dos CSV foram avaliados 71 voluntários (57? 14 ?), utilizando o aparelho Oral chromeTM. Foram determinadas as concentrações de proteína total, cálcio, fosfato, amilase e ureia em 171 voluntários (125? 46 ?), em saliva stim/unst. A bioquímica salivar foi semelhante em relação à antropometria. No entanto, as respectivas concentrações diferiram significativamente entre saliva Stim/Unst, com exceção da amilase. Os indivíduos apresentaram quantidades semelhantes de CSV em relação ao IMC. Em indivíduos com valores críticos de metilmercaptana (CH3SH) observou-se correlação significativa (r=0.51) com o pH (unst). Capítulo 3: Investigou o eventual aparecimento de adipócitos nas glândulas salivares em modelo animal (camundongos). A adipogênese foi realizada com dieta rica em gordura, e ainda via receptor de proliferadores de peroxissoma gamma (PPAR gama) com rosiglitazona. Western blot, histoquímica e imunoistoquímica foram utilizadas. Análise de microarray foi realizada para verificar o efeito da dieta. Anticorpos: fosfo-4E BP1 e tirosina hidroxilase marcaram a atividade de mTOR e nervos, respectivamente. O microarray mostrou um número significativo de alterações genéticas. Em relação à dieta observou-se baixa ou nenhuma expressão de fosfo 4E-BP1 e aumento na atividade de tirosina hidroxilase. Em camundongos tratados com rosiglitazona verificou-se ativação de mTOR e tirosina hidroxilase. Conclusão: Pelos resultados dos três capítulos concluiu-se que em indivíduos jovens e saudáveis a função mastigatória e paladar não foram influenciados pelo padrão salivar e foram fracamente relacionados ao antropométrico. A bioquímica salivar e presença de CSV foi semelhante em relação à antropometria. Observaram-se mudanças relacionadas à atividade do sistema nervoso em glândula salivar de camundongos devido à dieta rica em gordura ou ativação de PPAR gamma
Abstract: This study investigated masticatory function, the presence of volatile sulfur compounds (VSC) and salivary biochemistry in healthy subjects (18-33 years), and also the induction of adipocytes in the salivary gland and its implication in an animal model. Three studies were conducted, presented as chapters. Chapter 1: Investigated the performance and chewing ability, taste, and the possible relationship to gender, body mass index (BMI), waist circumference (WC) and stimulated salivary flow (Stim) and unstimulated (Unst). 171 individuals (125? 46?) were evaluated. Masticatory performance was determined by the ability of fragmentation Optocal plus and chewing ability with the use of visual analogue scale (VAS). Taste was verified by the perception of the four primary flavors. Descriptive statistics, normality tests, correlation, comparison and multiple linear regression models were used. In multiple linear regression performance was not predict by the independent variables in the model. With chewing ability the model explained 14% of variability and 5% for the taste. The results indicated that masticatory performance was not related to anthropometric parameters and saliva in healthy young subjects. The ability was related to BMI, WC and Gender. Taste was weakly related to BMI and WC. Chapter 2: Verify the salivary biochemistry and presence of VSC and the possible influence of BMI, flow and pH (Stim)/(Unst). For the verification of VSC 71 volunteers (14 57? ?) were assessed using the Oral chromeTM device. The concentrations of: total protein, calcium, phosphate, urea and amylase were investigated in 171 volunteers (46 125? ?) in saliva (Stim) / (Unst). Biochemical salivary were similar in respect of anthropometry. However, the concentrations differed significantly between saliva (Stim)/(Unst), with the exception of amylase. The sample presented similar amounts of CSV in relation to BMI. In individuals with critical values of methylmercaptan (CH3SH) we observed a significant correlation (r = 0:51) with pH Unst. The results indicate that in healthy young subjects salivary biochemistry and VSC exhibit similar behaviour in relation to BMI. The (CH3SH) when greater than the normal limit concentration was correlated to pH Unst. Chapter 3: We investigated the possible appearance of adipocytes in the salivary glands in animal model (mice). Adipogenesis was performed with high-fat diet, and also via peroxisome proliferator-gamma (PPAR gamma) with rosiglitazone . Western blot, histochemistry and immunohistochemistry were used. Microarray analysis was performed to assess the effect of diet. Antibodies: phospho-4E-BP1 and tyrosine hydroxylase marked mTOR and nerves activity, respectively. The microarray showed a large number of genetic changes. Regarding diet was observed low or no expression of phospho-4E-BP1 and an increase in tyrosine hydroxylase activity. In mice treated with rosiglitazone there was activation of mTOR and tyrosine hydroxylase. The results suggest that there are changes in salivary gland innervation before stimuli for adipogenesis. Conclusion: We concluded that in healthy young individuals masticatory function was not influenced by the salivary pattern and was weakly related to anthropometric. Salivary Biochemical and presence of CSV was similar in relation to anthropometry. There are alterations in the activity of the nervous system in the salivary glands of mice due high fat diet or activation of PPAR gamma
Doutorado
Anatomia
Doutora em Biologia Buco-Dental

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Guo, Heng. "Glucocorticoid induced leucine zipper is required for adipogenesis and is a target for the anti-adipogenic activities of oncostatin m." Thesis, Boston University, 2013. https://hdl.handle.net/2144/11007.

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Thesis (Ph.D.)--Boston University
Fat cell development is a dynamic cellular transition process in which committed preadipocytes convert to adipocytes. The initial goal of my research was to identify repressed gene programs in adipogenesis, and to test the hypothesis that these repressed gene programs suppress adipogenesis. Using microarray analyses of 3T3-L1 cells, we found that the expression of gene programs, most notably cytokines/chemokines, correlated inversely with the differentiation state. We analyzed the effect of different components of the adipogenic hormonal cocktail in 3T3-L1 preadipocytes. It was found that dexamethasone (Dex) acting through the glucocorticoid receptor (GR) was a major suppressor of the cytokine expression. In our efforts to characterize roles for glucocorticoid signaling in adipogenesis, we found that glucocorticoid-induced leucine zipper (GILZ), a target of GR, was required for adipogenesis in both 3T3-L1 preadipocytes and C3H10T1/2 mesenchymal stem cells (MSCs). We also showed that GILZ was required for bone morphogenic protein 4 (BMP4)-induced white adipocyte differentiation and BMP7-induced brown differentiation in C3H10T1/2 MSCs. In a gain-of-function study, GILZ overexpression (OE) had minimal effects on normal adipogenesis in 3T3-L1 preadipocytes, but increased adipogenic gene expression in C3H10T1/2 MSCs. Oncostatin M (OSM) is an anti-adipogenic cytokine. When exploring mechanisms governing the anti-adipogenic activity of OSM and testing the hypothesis that GILZ is a target for OSM, we found that while OSM inhibited the expression of endogenous GILZ, ectopically expressed GILZ overrode OSM's effect in suppressing adipocyte development, suggesting GILZ is a target of the anti-adipogenic activity of OSM. During our studies to find signaling pathways regulating the interplay between GILZ and OSM, we found that OSM induced both ERK and STAT5 phosphorylation, but only inhibition of ERK activity by U0126 partially abolished OSM's inhibition on GILZ expression. Taken together, we identified a cytokine/chemokine program that is downregulated in adipogenesis. Dex-GR-GILZ signaling pathway played an essential role in suppressing the cytokine program and is required for adipogenesis. OSM inhibited adipogenesis by suppressing expression of GILZ, which is mediated by the activation of ERK phosphorylation. These findings highlighted the critical role of GILZ m adipogenesis and can contribute to combating metabolic disorders such as obesity.

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SILVESTRINI, ANDREA. "Anti-inflammatory and anti-adipogenic activity of olive leaf extract and its bioactive compounds." Doctoral thesis, Università Politecnica delle Marche, 2022. https://hdl.handle.net/11566/299341.

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Le foglie d’olivo sono un materiale di scarto dell’industria dell’olio di oliva, uno degli alimenti alla base della dieta mediterranea. Negli ultimi anni la ricerca scientifica si è soffermata sulla possibilità di un riutilizzo di questo materiale data la sua ricchezza di composti bioattivi potenzialmente applicabili in ambito biomedico. Lo scopo di questo studio è stato quello di caratterizzare e valutare l’effetto anti-infiammatorio e anti- adipogenico di un estratto acquoso di foglie di olivo (OLE). L’estratto, prodotto nel nostro laboratorio a partire da foglie essiccate raccolte da coltivazioni senza uso di diserbanti e pesticidi, è stato caratterizzato per il contenuto di composti fenolici (569,5±22,142 µg/mL in termini di Total Phenol content) per poi essere testato in vitro su modelli cellulari di infiammazione acuta e cronica e differenziamento adipogenico. In particolare l’effetto in acuto è stato analizzato in colture primarie di cellule umane endoteliali (Human umbilical vein endothelial cell, HUVEC) e in una linea monocitica umana (THP1) trattate con LPS. I risultati ottenuti mostrano una riduzione sia della tempesta citochinica che dell’espressione delle molecole di adesione, la cui funzione nel processo infiammatorio è quella di favorire l’ulteriore reclutamento di cellule infiammatorie nel circolo. Le stesse HUVEC, ma in senescenza replicativa, sono state studiate come modello di infiammatoria cronica, l “inflammaging” che a sua volta è associata all’insorgenza delle malattie età- associate. Anche in questo caso l’estratto inibisce la produzione di quelle citochine che caratterizzano il fenotipo SASP (Senescence associated secretory phenotype). Infine, dato che l’accumulo del grasso midollare è una caratteristica comune in diverse patologie legate all’invecchiamento, e che il tessuto adoposo contribuisce allo stato infiammatorio sistemico dell’organismo, abbiamo valutato se l’estratto di foglie di olivo fosse in grado di inibire il differenziamento delle cellule stromali midollari umane (MSC) in senso adipogenico. Anche in questo caso abbiamo ottenuto risultati promettenti. In una seconda fase abbiamo analizzato sugli stessi modelli anche gli effetti di diversi principi attivi contenuti in OLE e purificati nel laboratorio diretto dal Prof Antonio Procopio dell’Università Magna Graecia, uno dei principali esperti al mondo sui principi attivi dell’olivo. Due di questi, l’oleaceina e l’oleuropeina-aglicone hanno effetti simili a quelli dell’estratto totale anche se quest ultimo è sempre più efficace del singolo principio attivo. La ricerca proseguirà col testare gli effetti di questi stessi principi attivi microincapsulati in particelle di materiali biocompatibili e mucoadesive (chitosano o acido ialuronico) da somminsitrare per areosol a soggetti con Covid al fine di ridurre la tempesta citochinica secondo quanto descritto nel progetto FISR2020 finanziato dal MUR, responsabile Prof.ssa Rippo, e di cui sono partecipante. Questo studio rappresenta infatti un primo passo relativo alla possibilità di poter considerare l’impiego di OLE e dei suoi composti come possibili coadiuvanti nelle terapie per diverse patologie sia acute che croniche. I risultati positivi ottenuti in modelli di infiammazione, senescenza e accumulo di grasso midollare, sono incoraggianti e stimolanti per proseguire la ricerca, confermare ed espandere le possibili implicazioni pratiche dell’uso di prodotti naturali per supportare il trattamento di diverse condizioni patologiche.
Olive leaves are a waste material from the olive oil industry, one of the staple foods of the Mediterranean diet. In recent years, scientific research has focused on the possibility of reusing this material because of its wealth of bioactive compounds that can be potentially applied in the biomedical field. the aim of this study was to characterise and evaluate the anti-inflammatory and anti-adipogenic effect of an aqueous olive leaf extract (OLE). The extract, produced in our laboratory from dried leaves harvested from herbicide- and pesticide-free cultivations, was characterised for its phenolic compound content (569.5±22.142 µg/mL in terms of Total Phenol content) and then tested on in vitro cellular models of acute and chronic inflammation and adipogenic differentiation. In particular, the acute effect was analysed in primary cultures of human umbilical vein endothelial cells (HUVEC) and in a human monocytic line (THP1) treated with LPS. The results obtained show a reduction in both the cytokine storm and the expression of adhesion molecules, whose function in the inflammatory process is to promote further recruitment of inflammatory cells into the circulation. The same HUVECs, but in replicative senescence, have been studied as a model of chronic inflammation, 'inflammaging' which in turn is associated with the onset of age- related diseases. Again, the extract inhibits the production of cytokines that characterise the SASP (Senescence associated secretory phenotype). Finally, given that accumulation of bone marrow fat is a common feature of several age-related diseases, and that adoptive tissue contributes to the body's systemic inflammatory state, we assessed whether OLE could inhibit the differentiation of human bone marrow stromal cells (MSCs) in an adipogenic direction. Again, we obtained promising results. In a second phase, we also analysed the effects of several active compounds contained in OLE and purified in the laboratory directed by Prof Antonio Procopio of the Magna Graecia University, one of the world's leading experts on olive tree active compounds. Two of these, oleacein and oleuropein-aglycone, have effects similar to those of the total extract, although the latter is always more effective than the single active compound. The research will continue by testing the effects of these same active ingredients microencapsulated in particles of biocompatible and mucoadhesive materials (chitosan or hyaluronic acid) that can be administered by areosol to subjects with Covid in order to reduce the cytokine storm as described in the FISR2020 project funded by the MUR, responsible Prof. ssa Rippo, and in which I am a participant. This study represents a first step towards the possibility of considering the use of OLE and its compounds as possible adjuvants in therapies for various acute and chronic diseases. The positive results obtained in models of inflammation, senescence and bone marrow fat accumulation are encouraging and stimulating for further research, confirming and expanding the possible practical implications of using natural products to support the treatment of different pathological conditions.

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Arçari, Demétrius Paiva 1978. "Avaliação da erva-mate (Ilex paraguariensis) na adipogênese e sinalização da insulina." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317039.

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Orientador: Marcelo Lima Ribeiro
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A obesidade e considerada um problema de saúde publica, principalmente pelo fato desta estar associada com diversas patologias como a resistência a insulina (RI). Atualmente, diversas estratégias são utilizadas visando a redução de peso corporal, dentre estas se destaca o uso de produtos de origem vegetal, incluindo a Ilex paraguariensis, cujo nome comum e erva-mate. Muitos trabalhos mostram que os compostos detectados na erva-mate possuem diferentes funções biológicas, tais como: ação antioxidante, antiinflamatória, imunomodulatoria, anticancerígena, modificação do metabolismo de colesterol, entre outros. Muito embora diversos estudos destaquem as funções biológicas da erva-mate, pouco se sabe sobre sua capacidade de modulação na expressão de genes relacionados a obesidade, e seu efeito na via de sinalização da insulina. Deste modo o presente estudo teve como objetivo avaliar a ação do extrato aquoso de erva-mate tostado no processo de adipogênese e sua ação nos mecanismos de sinalização da insulina. Os dados do presente trabalho mostram que a erva-mate na concentração de 1,0g/kg em animais submetidos a dieta hiperlipídica aumentou a expressão de diferentes genes responsáveis pela ativação da AKT, reduziu a translocação nuclear de NF-kB e FOXO1, reduziu a expressão PEPCK e G6Pase ligados ao processo de gliconeogênese no tecido hepático. Os efeitos da erva-mate na sinalização da insulina foram ratificados, por analise protéica de IRS-1, IRS-2 e AKT, redução na resistência a insulina observada pelo teste do KITT e redução da glicemia basal. O presente trabalho demonstra ainda em cultura celular de 3T3-L1 que a erva-mate e alguns de seus principais compostos bioativos (ácido clorogênico, rutina e quercetina), possuem ação mais expressiva na etapa de diferenciação do adipócito e atuam modulando distintos genes relacionados ao processo de diferenciação do adipócitos. O trabalho ainda sugere que a erva-mate possa atuar in vitro e ex vivo de maneira mais expressiva na redução da adipogênese através da via WNT, visto pelo aumento da expressão de diferentes genes relacionados com essa via. O resultado final da ativação desta via e a repressão significativa de PPARy2 e C/EBP'alfa', principais fatores de transcrição necessários para que ocorra a etapa final do processo de diferenciação dos adipócitos, contribuindo assim para elucidar a redução do peso corpóreo e da gordura epididimal observada nos animais submetidos a dieta hiperlipídica tratados com erva-mate durante 60 dias, que por sua vez reduz a produção de citocinas, em especial o TNF-'alfa', contribuindo parcialmente para a melhora do quadro de sinalização a insulina observado apos intervenção
Abstract: Obesity is a problem of public health, mainly because it is associated with many conditions such especially insulin resistance (IR). Currently, several strategies have been used in order to reduce the total body weight, among these there is a growing evidence supporting the use of products of plant origin, including the Ilex paraguariensis, whose common name is yerba mate. Various studies have shown that the compounds found in yerba mate has several biological functions, such as antioxidant, anti-inflammatory, immunomodulatory, anticancer, modification of cholesterol metabolism and others. Although several studies highlight the biological functions of yerba mate, there are lack of evidence providing their ability to modulate expression of genes related to obesity and its effect on the insulin signaling pathway. Thus, the aim of this study was to evaluate the effects of yerba mate in gene expression that regulate adipogenesis and insulin signaling pathway. Our data showed yerba mate (1,0 g/kg) in animals subjected to high fat diet, increased different gene expression responsible for the activation of the AKT, reduction of FOXO1 and NF-kB nuclear translocation, reduction gene expression of PEPCK and G6Pase involved in gluconeogenesis process in liver. The effects of yerba mate in insulin signaling was confirmed by IRS-1, IRS-2 and AKT protein analysis, reduction in insulin test tolerance by KITT and reduction in glucose. Our data also showed in 3T3-L1 cell culture that yerba mate and some of its major bioactive compounds (chlorogenic acid, rutin and quercetin), act in an early stage of adipocyte differentiation and modulate different gene expression that regulate adipogenesis. Additionally, yerba mate can act in vitro and ex vivo in WNT pathway, seen by the increased expression of different genes in this pathway resulting in a significant repression of C/EBP'alfa' and PPARy2, the most important transcription factors essencial for the occurrence of adipocyte differentiation. This findings collaborate to elucidate the reduction of body weight and epididymal fat observed in animals subjected to high fat diet treated with yerba mate for 60 days, which reduces the production of cytokines, particularly TNF-'alfa', contributing partially to the improvement in insulin signaling observed after intervention
Doutorado
Genetica Animal e Evolução
Doutor em Genetica e Biologia Molecular

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Pastel, Emilie. "Rôles des aldose réductases dans l'homéostasie des tissus adipeux blancs humains et murins." Thesis, Clermont-Ferrand 2, 2014. http://www.theses.fr/2014CLF22492/document.

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Les aldose réductases (AKR1B) sont des oxydoréductases dépendantes du NADPH initialement décrites pour leurs fonctions de détoxication cellulaire et de réduction du glucose. La découverte de l’expression d’Akr1b7 dans le tissu adipeux murin ainsi que l’activité prostaglandine F2α synthase (PGFS) spécifique de certaines isoformes suggèrent des rôles biologiques inédits pour ces enzymes. La prostaglandine F2α (PGF2α) inhibant l’adipogenèse, cette fonction PGFS met en avant l’implication des AKR1B dans la physiologie du tissu adipeux blanc (TAB). L’objectif de ces travaux était de caractériser l’expression de l’ensemble des AKR1B au sein des TAB murins et humains et de comprendre leur impact sur l’homéostasie du tissu adipeux et en particulier sur l’adipogenèse et la lipolyse. Nous avons montré que l’ensemble des AKR1B était exprimé dans le TAB murin. Akr1b3, Akr1b8 et Akr1b16 sont exprimées à la fois dans les fractions stroma‑vasculaires (contenant des cellules immunitaires, vasculaires, progénitrices…) et adipocytaires. A l’inverse, Akr1b7 n’est pas exprimé par les adipocytes. Les analyses réalisées in vitro indiquent qu’à l’exception d’Akr1b16, les isoformes murines des AKR1B voient leur expression augmenter précocement et transitoirement au cours de l’adipogenèse. Chez l’homme, l’isoforme AKR1B1 est exprimée dans le TAB sous‑cutané de patients obèses alors qu’AKR1B10 est difficilement détectable (western blot, RT‑qPCR). In vitro, l’expression d’AKR1B1 augmente tout au long de la différenciation adipocytaire contrairement à AKR1B10 qui est préférentiellement exprimé dans les cellules indifférenciées. L’utilisation d’un inhibiteur spécifique des AKR1B montre que l’activité PGFS d’AKR1B1 constitue un frein à l’adipogenèse. Nous montrons aussi que les mécanismes régulant l’action de la PGF2α diffèrent en fonction des espèces. Chez l’homme, l’expression du récepteur FP est régulée dans le temps alors que dans les cellules murines, c’est l’expression des PGFS et donc la synthèse de PGF2α qui définit, au cours de l’adipogenèse, la fenêtre d’action de cette prostaglandine. Les souris invalidées pour la PGFS Akr1b7 présentent une diminution des quantités intra‑tissulaires en PGF2α associée à une expansion accrue de leurs tissus adipeux due à une augmentation de l’adipogenèse et à une hypertrophie adipocytaire sans modification de l’expression des enzymes impliquées dans la lipogenèse (Volat et al., 2012). Ces données en accord avec le rôle anti‑adipogénique de la PGF2α suggèrent aussi une action sur la lipolyse. Nous démontrons ici que la perte d’Akr1b7 entraîne une diminution de l’activité lipolytique du TAB. L’utilisation de cellules murines (3T3‑L1) et humaines (hMADS) différenciées en adipocytes, nous a permis de montrer que la stimulation de l’activité lipolytique suite à l’activation du récepteur FP résultait en partie d’une augmentation de la phosphorylation de HSL (forme active) et de l’accumulation de la lipase ATGL. Le troisième volet de ce travail de thèse a consisté à caractériser un modèle de souris transgénique surexprimant AKR1B1 dans le TAB (souris aP2‑AKR1B1) afin d’étudier le rôle biologique de cette isoforme humaine
Aldose reductases are NADPH-dependent oxydoreductases described for their involvement in cellular detoxification and glucose reduction. The discovery of Akr1b7 expression in murine adipose tissue together with the prostaglandin F2α Synthase (PGFS) activity of some isoforms suggest unreleased biological roles for these enzymes. Prostaglandin F2α (PGF2α) inhibiting adipogenesis, this PGFS function highlights AKR1B potential involvement in white adipose tissue (WAT) physiology. This work aimed at characterising the expression of all AKR1B in both murine and human WAT and understanding their impact on adipose tissue homeostasis and especially on adipogenesis and lipolysis. We showed that all AKR1B were expressed in murine WAT. Akr1b3, Akr1b8 and Akr1b16 were both expressed in the stromal vascular fraction (containing immune cells, vascular cells, progenitors…) and in the adipose fraction. In contrast, Akr1b7 was not expressed in adipocytes. In vitro analyses indicated that, except for Akr1b16, murine AKR1B isoform expression increased early and transiently during adipogenesis. In human, AKR1B1 was expressed in human subcutaneous WAT from obese patients whereas AKR1B10 was hardly detectable (western blot, RT‑qPCR). In vitro, AKR1B1 expression increased throughout adipocyte differentiation unlike AKR1B10, which was preferentially expressed in undifferentiated cells. Using an AKR1B specific inhibitor, we demonstrated that AKR1B1 PGFS activity was a dampen to adipogenesis. We also showed that mechanisms regulating PGF2α action differed according to the species. In human cells, the expression of FP receptor was time-regulated whereas, in murine cells, PGFS expression and thus, PGF2α synthesis, limited PGF2α activity during adipogenesis. Akr1b7 knockout mice have decreased PGF2α intratissular levels associated with an expansion of adipose tissue resulting from an increase of adipogenesis and an adipocyte hypertrophia without any modification of lipogenic enzymes expression (Volat et al., 2012). These data, in agreement with PGF2α anti-adipogenic action, suggest an impact on lipolysis. We demonstrated that loss of Akr1b7 led to a decrease of WAT lipolytic activity. The use of murine (3T3‑L1) and human (hMADS) differentiated cells allowed us to show that the stimulation of lipolysis in response to FP activation was, in part, due to an increase of HSL phosphorylation (active form) and an increase of ATGL accumulation. The third part of this work consisted in characterizing the phenotype of transgenic mice overexpressing AKR1B1 in WAT (aP2‑AKR1B1 mice) in order to study the biological role of this human isoform

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MacKay, Maria-Danielle L. "Characterization of Medullary and Human Mesenchymal Stem Cell-Derived Adipocytes." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1232775772.

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Barlette, Adriana Gregory. "Avaliação química e biológica do extrato hidroetanólico de erva-mate (ilex paraguariensis a. st. hil.)." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/31784.

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Ilex paraguariensis A. St.-Hil., conhecida como erva-mate, é uma árvore nativa da América do Sul onde as folhas e pequenos ramos secos são usados para preparar o chimarrão. Possui uma composição química complexa, da qual pode-se vislumbrar muitas aplicações potenciais, que poderiam vir a ampliar o emprego da erva-mate e, conseqüentemente, do mercado para esta matériaprima. As folhas de I. paraguariensis contem xantinas, flavonóides, derivados do ácido cafeoilquínico e uma quantidade significativa de saponinas triterpenóides (cerca de 10%). Neste estudo foram investigados quimicamente extratos hidroetanólicos de I. paraguariensis, de suas frações, e de algumas substâncias de referência, como também os efeitos desses na atividade antioxidante, no acúmulo de gordura (TG) e na atividade lipolítica em cultura de células 3T3-L1. Neste sentido obtivemos extratos brutos hidroetanólicos de folhas verdes (EBV) e secas (EBS) maceradas, os quais foram fracionados originando 8 frações. Ácido ursólico, ácido clorogênico e rutina foram quantificados por cromatografia líquida de alta eficiência (CLAE). Também foi realizada a determinação de fenóis por catequinas e pela precipitação por proteínas. A fração fenólicos da folha verde apresentou atividade antioxidante superior às substâncias de referência rutina e ácido clorogênico, enquanto que o ácido ascórbico apresentou a melhor atividade. O ensaio com brometo de 3- (4,5-dimetil)difenil tetrazólio (MTT) demonstrou que os extratos e padrões testados entre 50 μg/mL e 1000 μg/mL não foram citotóxicos para as células 3T3-L1. Dentre as frações testadas para a atividade na adipogênese, a fração resíduo aquoso da folha verde (RAV) apresentou maior inibição (24%) no teor de TG na concentração de 100 μg/mL. Dentre as substâncias de referência testadas, os melhores resultados foram obtidos com o ácido caféico nas concentrações de 300 μg/mL e da rutina na concentração de 100 μg/mL. Em relação à ativividade na lipólise, a fração RAV apresentou o melhor resultado nas concentrações de 50 e 75 μg/mL. Entre as substâncias de referência, o ácido gálico apresentou resultado significativo em relação à atividade antilipolítica nas concentrações de 500 e 1000 μg/mL. Para elucidar em qual estágio da adipogênese e da lipólise os extratos, frações e padrões atuam, são necessários a investigação da avaliação da ação desses extratos e frações através de análise de expressão de genes ligados a adipogênese e a atividade lipolítica.
Ilex paraguariensis A. St.-Hil., known as maté, is a native tree from South América which leaves and twigs are used to prepare the traditional beverage “chimarrão”. It has a complex chemical composition that might have many potential applications in order to increase the use of maté and then, in consequence, increase the market demand of this raw material. Leaves from I. paraguariensis have xanthines, flavonoids, cafeoylquinic acid derivatives and triterpenoid saponins (ca. 10%). Herein, it was investigated, both chemically and biologically, the hydroethanolic extracts of leaves from I. paraguariensis, its fractions, and some reference substances, as the antioxidant activity, the adipogenesis (TG) and lipolytic activities in 3T3-L1 cell culture. So, it was prepared hydroethanolic extracts of fresh (EBV) and dried leaves (EBS) by maceration, which submitted to further fractionation furnished 8 fractions. Ursolic acid, chlorogenic acid and rutin were determined in these samples by liquid chromatography (HPLC) Also, phenolic constituents were determined using catequines and protein precipitation methods. The phenolic fraction from fresh leaves presented better antioxidant activity than the tested reference substances (rutin and chlorogenic acid), while ascorbic acid presented the best activity. The MTT assay showed that the tested extracts and fractions among 50 μg/mL and 1000 μg/mL did not present citotoxicity to 3T3-L1 cells. Among the tested fractions to adipogenesis, the aqueous residue fraction from fresh leaves (RAV) presented best inibition (24%) of TG at 100 μg/mL. Among tested reference substances, cafeic acid at 300 μg/mL, and rutin at 100 μg/mL presented the best results. In relation to the lipolytic activity, the RAV fraction presented best results at 50 e 75 μg/mL and, among the tested reference substances, galic acid presented best results at 500 e 1000 μg/mL. In order to understand the mechanim of action of these fractions and reference substances at the adipogenesis and lipolysis further studies will be performed specially those about the influence on the gene expression.

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Muret, Kévin. "Annotation des ARN longs non-codants chez la poule et les espèces d’élevage : Focus sur les ARNlnc régulateurs du métabolisme des lipides." Thesis, Rennes, Agrocampus Ouest, 2018. http://www.theses.fr/2018NSARC139/document.

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L’annotation des génomes est un défi majeur pour lier les génotypes aux phénotypes. Identifier les ARN longs non-codants (ARNlnc) dans les génomes fait partie de ce défi ; d’expression relativement faible, ils n’ont été mis en évidence que récemment (2012) par l’avènement des technologies de séquençage haut débit. Ces travaux de recherche ont permis à partir de données RNA-seq, de mettre en lumière un grand nombre d’ARNlnc chez les espèces d’élevage et en particulier chez la poule chez qui aucun ARNlnc n’était décrit au début de cette thèse (2015). Un premier travail a consisté à identifier ces ARNlnc en utilisant des échantillons de foie et tissu adipeux puis nous avons amélioré ce catalogue par intégration d’autres bases de données publiques d’ARNlnc disparates. De plus, d’après la littérature, les ARNlnc ont été décrits comme intervenant dans la régulation de tous les processus biologiques :de la structure cellulaire à l’expression des gènes. La problématique de l’équipe étant associée à la compréhension de la régulation du métabolisme des lipides chez la poule, mon second travail a consisté à établir la liste des ARNlnc connus dans le règne animal comme étant impliqués dans ce métabolisme ou dans le processus de stockage et de formation du tissu adipeux, l’adipogenèse. Les analyses de conservation par synténie ont permis de retrouver une vingtaine de ces ARNlnc chez la poule. Enfin, à partir de lignées divergentes pour le poids de gras abdominal, j’ai également mis en évidence de nouveaux ARNlnc potentiellement régulateurs de ce métabolisme lipidique
Genome annotation is a major challenge in connecting genotypes with phenotypes. Identifying long noncoding RNAs (lncRNA) in genomes is part of this challenge; they are relatively low-expressed and have only been highlighted in 2012 thanks to the development of high throughput sequencing technologies. This research work has led to the identification of a large number of lncRNAs in livestock species, particularly in the chicken, in which no lncRNA had yet been described at the beginning of this thesis (2015). First, my aim was to identify these lncRNAs using liver and adipose tissue and to improve this catalogue by integrating other existing lncRNA public databases.Moreover, according to the literature, lncRNAs are involved in the regulation of any biological process, from gene expression to cell structure. One of the goals of our team is to understand the regulation of lipid metabolism in the chicken, I thus established the list of all lncRNAs known within the animal kingdom and involved in this metabolism or in adipogenesis, the process of storage and formation of adipose tissue. The conservation by synteny analyses revealed around twenty conserved lncRNAs in the chicken. From divergent abdominal fat weight chicken lines, I lastly identified new lncRNAs that potentially regulate this lipid metabolism

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Volat, Fanny. "Rôle des aldose réductases dans la physiologie du tissu adipeux blanc : modèles génétiques murins perte et gain de fonction." Phd thesis, Université Blaise Pascal - Clermont-Ferrand II, 2011. http://tel.archives-ouvertes.fr/tel-00686589.

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Le développement du tissu adipeux blanc est finement régulé par des facteurs pro- et anti- adipogéniques. Au cours de l'obésité, son expansion conduit à de nombreuses complications métaboliques. A ce jour, peu de données sont disponibles sur les facteurs qui contrôlent négativement son développement. Dans ce contexte, le laboratoire a dirigé ses recherches sur le rôle de l'aldose réductase murine Akr1b7 dans ce tissu. Akr1b7 est exprimée dans la fraction stromale vasculaire du tissu adipeux blanc et possède un effet anti-adipogénique sur les préadipocytes en culture. La réalisation et l'analyse de souris invalidées pour le gène Akr1b7 nous a permis de démontrer que la perte de Akr1b7 entraîne une expansion de la masse adipeuse par une hypertrophie et une hyperplasie des adipocytes associées à une insulino-résistance. Les souris Akr1b7-/- ne sont pas hyperphagiques mais présentent un métabolisme basal réduit. Akr1b7 qui possède une activité prostaglandine synthase, régule le développement excessif du tissu adipeux par deux mécanismes dépendant de la PGF2α à savoir, l'inhibition de l'adipogenèse et de la lipogenèse. D'autre part, nous avons développé un modèle de souris transgéniques sur-exprimant l'aldose réductase humaine AKR1B1 dans le tissu adipeux. Contre toute attente et à l'inverse de Akr1b7, ce modèle montre un effet pro-adipogénique deAKR1B1. Ces données in vivo révèlent des activités inédites et opposées entre différentes isoformes d'aldose réductase et ouvrent de nouvelles pistes pour appréhender les mécanismes contrôlant l'homéostasie adipeuse et ses dérèglements.

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Sertié, Rogério Antonio Laurato. "Repercussões do destreinamento físico sobre o metabolismo e a celularidade do tecido adiposo branco periepididimal de ratos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-10012011-164001/.

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Todas as adaptações adquiridas através do treinamento físico são reversíveis durante a inatividade. Reduções significativas no consumo máximo de oxigênio (VO2max) são observadas dentro de duas a quatro semanas de destreinamento. Por outro lado, as consequências do destreinamento sobre o tecido adiposo são pouco estudadas. O objetivo foi investigar os efeitos de destreinamento físico sobre o metabolismo e celularidade do tecido adiposo periepididimal. Métodos e Resultados: Ratos Wistar machos, com idade de 6 semanas, foram divididos em 3 grupos: treinado (T) durante 12 semanas; destreinados (D), (treinados por 8 semanas e destreinados por 4 semanas), e sedentário (S) pareados por idade. O treinamento consistiu em sessões de esteira rolante (1h/dia, 5d/semk, 50 60% da capacidade máxima). A análise morfométrica do tecido PE revelou diferenças significativas entre os grupos. A área seccional dos adipócitos do grupo D foi significativamente maior que a T e S (3474 µm2 ± 68,8 µm2 vs 1945,7 µm2 ± 45,6 µm2 vs 2492,4 µm2 ± 49,08 µm2, respectivamente). Em comparação com as células dos animais do grupo T as células do D apresentaram 48% de aumento na capacidade de realizar a lipogênese, espontaneamente ou insulina estimulada. Já lipólise basal não se alterou. A redução de 15% na apoptose foi observada nos grupos T e D em relação ao S. Algumas expressões de genes foram alterados em D vs S: a adiponectina aumentou 3 vezes e PPAR-gama aumentou 2 vezes. O gene do Pref-1 foi 3 vezes maior em T vs S. Estes resultados sugerem fortemente que a adipogênese foi estimulada neste grupo. Conclusões: o destreinamento causa aumento significativo no tamanho dos adipócitos e na capacidade lipogênica. Como a apoptose celular na gordura PE foi reduzida em D e T, estes resultados sugerem que as alterações do tecido adiposo após destreinamento podem ser potencialmente obesogenicas.
All adaptations acquired through physical training are reversible during inactivity. Significant reductions in maximal oxygen uptake (VO2Max) are observed within two-four weeks of detraining. Conversely, the consequences of detraining on adipose tissue are poorly known. The objective was to investigate the physical detraining effects on metabolism and cellularity of rat periepididymal adipose tissue. Methods and Results: Male Wistar rats, ageing 6 weeks, were divided in 3 groups: trained (T) for 12 weeks; detrained (D), (trained for 8 weeks and detrained for 4 weeks), and age-matched sedentary (S). Training consisted in treadmill running sessions (1h/day, 5d/week, 50 60% of the maximal capacity). The morphometric analysis of PE tissue disclosed significant differences between the groups. The adipocyte sectional area of group D was significantly bigger than T and S (3474 µm2 ± 68,8 µm2 vs 1945,7 µm2 ± 45,6 µm2 vs 2492,4 µm2 ± 49,08 µm2, respectively). Compared to T the cells of D animals showed 48% increased ability to perform: lipogenesis, either spontaneously or insulin stimulated and isoproterenol-stimulated lipolysis. Basal lipolysis did not change. A 15% reduction in apoptosis was observed in groups T and D in relation to S. Some gene expressions were changed in D vs S: adiponectin (3-fold up) and PPAR-gamma (2-fold up). PREF-1 gene was 3-fold higher in T vs S. These results strongly suggest that adipogenesis was stimulated in this group. Conclusions: Detraining causes significant increase in adipocyte size and lipogenic capacity. As PE fat cell apoptosis was reduced in D and T, these results suggest that adipose tissue changes following detraining can potentially be obesogenic.

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Estrada, Marta Maria Vieira Matutino Falcão. "The role of gliptins on adipogenesis." Master's thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/10732.

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Dissertação elaborada com vista à obtenção do Grau de Mestre em Biotecnologia
This work was performed at the Neuroendocrinology and Neurogenesis Group at the Center for Neurosciences and Cell Biology of the University of Coimbra, and financed by FCT (PTDC/SAUFCF/102415/2008) and FEDER

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Boulet, Nathalie. "Rôles des Bone Morphogenetic Proteins dans la conversion adipocytaire et le développement du tissu adipeux humain." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30187/document.

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Les adipocytes (cellules spécialisées dans le stockage des graisses) sont formés à partir de cellules immatures appelées cellules progénitrices lors du processus d'adipogenèse. Chez l'homme, les différentes étapes de ce processus sont mal connues ainsi que les signaux qui le régulent. La première partie de mon travail de thèse a eu pour but de caractériser la cellule intermédiaire entre la cellule progénitrice et l'adipocyte : le préadipocyte. La deuxième partie a consisté à évaluer le rôle des protéines morphogénétiques de l'os (ou BMP), des inducteurs de l'adipogenèse décrits chez la souris, dans l'adipogenèse humaine. Nous avons montré que les BMP2, 4 et 7 sont produites dans le tissu gras humain et BMP7 est modulée par l'obésité. Les BMP2 et 4 induisent l'adipogenèse des cellules progénitrices humaines mais seule la BMP7 permet la production d'adipocytes particuliers " beiges " décrits pour consommer les lipides et produire de la chaleur. Ces travaux affinent nos connaissances sur les mécanismes impliqués dans l'expansion du tissu gras et permettront d'élaborer des stratégies pour lutter contre le développement des pathologies liées à l'obésité
Adipocytes (cells specialized in fat storage) arise from immature cells, called progenitor cells, during the process of adipogenesis. In human, the different stages of adipogenesis are not well defined as well as the signals involved in adipogenic modulation. The first part of my thesis work aimed to characterize the intermediate cell state between progenitor cell and mature adipocyte: the preadipocyte. The second part aimed to evaluate the role of bone morphogenetic proteins (BMPs) in human adipogenesis. In mice, BMP2 and BMP4 induce classical adipogenesis whereas BMP7 leads to the production of "brite" adipocytes with the capacity to use lipids to produce heat. We have shown that BMP2, 4 and 7 are produced in human fat depots and BMP7 is modulated by obesity. BMP2 and 4 induce classical adipogenesis and BMP7 only induces brite adipogenesis from human progenitor cells. These works improve our knowledge about the mechanisms involved in the expansion of fat depot and may allow the identification of new strategies to fight against the development of obesity-associated pathologies

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Stillitano, Alexia. "miR-34a : a key regulator of adipogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206552.

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Introduction Globesity, the worldwide obesity epidemic, represents a major threat and public health burden. An uncontrolled expansion of the adipose tissue followed by a chronic low-grade inflammation leads to the dysfunction of the adipose organ resulting in obesity and its associated metabolic complications. Uncovering the mechanisms of adipogenesis, the development of adipocytes, therefore strikes as a key strategy in combating the disease. MicroRNAs (miRs), a class of small non-coding RNAs, have emerged in recent years as crucial modulators of diverse biological processes such as cell proliferation, differentiation, and signal transduction emphasizing their large potential as targets. Numerous miRs have been associated with the adipose tissue and metabolism and their dysregulation has repeatedly been linked to diseases including diabetes and obesity. This study aimed to investigate the role of miR-34a, an obesity-related miR, in the regulation of pre-adipocyte differentiation. Materials and Methods Mouse 3T3-L1 pre-adipocytes were employed as an in vitro system to study adipogenesis. Oil Red O staining served to evaluate the degree of adipogenesis and the over-expression of miR-34a in adipocytes was achieved by a lentiviral system. MiR and messenger RNA (mRNA) levels were analysed using TaqMan and SYBR Green-based quantitative real time PCR (qPCR) respectively. Results The expression of miR-34a was substantially down-regulated upon treatment of differentiation medium for two days and remained significantly low during the differentiation period compared with undifferentiated pre-adipocytes. Lentivirus-mediated over-expression of miR-34a successfully up-regulated miR-34a. Higher levels of miR-34a in turn mitigated adipogenesis as evidenced by blunted Oil Red O staining. This observation was found to be in good agreement with the qPCR analysis, which showed a down-regulation of several key adipogenic markers. Conclusion The down-regulation of miR-34a is required during pre-adipocyte differentiation for the efficient proceedings of the adipogenic programme. Further investigation is needed to evaluate the potential therapeutic implication of miR-34a-based treatment in managing obesity.
published_or_final_version
Medicine
Master
Master of Medical Sciences

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17

Pereira, Angélica Costa Aranha Camacho 1976. "Efeito de um bloqueador do receptor PDGF na adipogênese de camundongos tratados com dieta hiperlipídica." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311204.

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Orientador: Mario Jose Abdalla Saad
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A obesidade é hoje considerada um problema de saúde pública. Essa condição é caracterizada pelo aumento do peso corporal, mais especificamente do tecido adiposo branco. A adipogênese (diferenciação do pré-adipócito em adipócito) é um fenômeno complexo e não muito bem caracterizado. Recentes estudos mostraram que os préadipócitos estão localizadas nas paredes dos vasos que irrigam o tecido adiposo. Estas células estão presentes exclusivamente neste tecido e expressam alguns marcadores, dentre eles o PDGFRß. O PDGFRß é um receptor tirosina quinase cujo papel na migração, proliferação e diferenciação de diversos tipos celulares tem sido extensivamente estudado. O AG1296 (6,7- dimetoxi-2-fenil-quinoxalina) é um potente inibidor do receptor PDGF, pertencente à classe da quinoxalinas. Deste modo, levando-se em consideração o papel do receptor PDGF no crescimento e proliferação celulares e o fato de que as células PDGFR_ positivas provenientes do tecido adiposo possuem alto potencial adipogênico, neste estudo investigamos o efeito do AG1296 na adipogênese de camundongos submetidos à dieta hiperlipídica e à dieta padrão. Nós também investigamos se essa inibição afetaria a sensibilidade à insulina desses grupos estudados. Para tanto, camundongos Swiss machos com seis semanas de vida foram divididos em quatro grupos: o grupo Controle que recebeu dieta padrão, o grupo C+AG1296 que recebeu dieta padrão e tratamento com AG1296, o grupo DH que recebeu dieta hiperlipídica somente e o grupo DH+AG1296 que recebeu dieta hiperlipídica e tratamento com AG1296. Peso corpóreo e ingestão alimentar foram medidos diariamente durante o tratamento (7 ou 15 dias). Através de Western blot, foram quantificadas as principais proteínas pró-adipogênicas (SREBP-1c, C/EBP? e PPAR?) e a fosforilação das principais proteínas da via da insulina (IR, IRS1 e AKT). Nossos resultados indicaram que nos animais controle, após 15 dias de tratamento com AG1296, houve uma redução nas três frações de tecido adiposo, associada a uma redução em algumas das proteínas adipogênicas, além de uma melhora na sinalização insulínica em fígado e músculo e uma redução na glicemia de jejum. Além disso, nos animais submetidos à dieta hiperlipídica, após 7 dias de tratamento com AG1296, foi possível observar uma redução nas proteínas adipogênicas e uma redução na fração epididimal do tecido adiposo. Houve também uma melhora na sinalização insulínica e na tolerância à glicose. Com isso, podemos sugerir que a inibição do PDGFRß pode ter um papel importante na adipogênese e na sinalização insulínica e pode ser um alvo potencial para prevenção da obesidade e resistência à insulina
Abstract: Obesity can be defined as a disease in which body fat is excessively accumulated. Adipogenesis is a complex and not completely known phenomenon. Recent studies showed that adipocyte progenitor cells are exclusively found in adipose tissue and express some markers like PDGFRß (Platelet-derived growth factor ß). AG1296 (6,7-dimethoxy-2-phenyl-quinoxaline) is a potent and selective inhibitor of PDGF receptor kinase. In this context, the main objective of this work was to investigate if the inhibition of PDGF receptor through AG1296 would be able to affect white adipose tissue generation in high-fat-diet-fed and standard-chow-fed mice. We also investigated if this inhibition would have an effect on the insulin sensitivity in these studied groups. For this purpose, six-week-old male Swiss mice were divided into four groups and assigned to receive the following diet and/or treatment: the control group (C) received standard rodent diet, the second group (C + AG1296) received standard rodent diet plus AG1296 (50 mg/Kg/day by gavage), the third group (HFD) received high fat diet (55% calories from fat, 29% calories from carbohydrate and 16% from protein) and the fourth group (HFD+AG1296) received high fat diet plus AG1296. Body weight and food intake were measured during the treatment (7 and 15 days). After that, tissues (epididymal, retroperitoneal and mesenteric adipose tissue, liver and muscle) were extracted and processed. Through Western blot analysis, we were able to quantify the main proteins related to adipogenesis (SREBP-1c, C/EBP? e PPAR?) and the phosphorylation of the main proteins from insulin pathway (IR, IRS1 and Akt). Our results indicated that on control mice, after 15 days of treatment with AG1296, there was a reduction on adipose fat pad, associated with reduction in some adipogenic proteins, an increase in insulin signaling in liver and muscle and a reduction in fasting plasma glucose. Futhermore, on mice fed a high fat diet, after 7 days of treatment with AG1296, it was possible to observe a reduction on adipogenesis proteins and a reduction in epididymal fat pad. Also, there was an improvement in insulin signaling pathway and in glucose tolerance. In conclusion, our results suggest that PDGFRß inhibition might have an important role in adipogenesis and in insulin signaling and could be a potential target for preventing obesity and insulin resistance
Mestrado
Biologia Estrutural, Celular, Molecular e do Desenvolvimento
Mestre em Ciências

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18

Sharafi, Parisa. "The Effect Of Mechanical Forces On Adipogenic Differentiation." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/12609224/index.pdf.

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Numerous intra and extra cellular factors take role in differentiation of cell towards a given lineage. These factors have crucial role in cell-cell and cell-environment interactions. In this study, the aim is to investigate the effect of mechanical forces on the adipogenic differentiation of preadipocytes and mesenchymal stem cells in an in vitro model. Human preadipocytes and mesenchymal stem cells were embedded in 2 % agarose discs. According to the stress-relaxation test results it was observed that initial mechanical properties of agarose-mesenchymal stem cell (MSC) discs did not change compared to acellular agarose whereas those of preadipocytes decreased significantly. The discs with cells were exposed to compression under different weights (1.4 ±
0.2 g, 7.5 ±
0.2 g, and 14.6 ±
0.3 g.) continuously in differentiation medium for 21 days. The control discs were treated with differentiation medium without any compressive weight on top of them. After 21 days, total ribonucleic acids (RNA) have been isolated. Adipogenic differentiation was investigated via reverse transcription coupled quantitative polymerase chain reaction (PCR). The expression of peroxisome proliferators-activated receptors (PPAR-gamma), CCAAT-enhancer binding protein (C/EBP-Beta), leptin, adiponectin, adipophilin and human stearoyl-CoA desaturase (hSCD) have been assessed as adipogenic markers. Differentiation to adipocytes has been further investigated by histochemical Sudan IV staining and immunochemistry and compared to control group. Decrease in the expression of adipogenic factors, size and number of lipid droplets were observed for both MSCs and preadipocytes subjected to compression in agarose discs. The decreases were correlated with the level of mechanical stress. The highest depletion of gene expression was observed in leptin and C/EBP&
#61538
. From our results, it was shown for the first time that mechanical stress impaired the adipogenic differentiation of MSCs and preadipocytes in agarose discs. However, the differentiation pathways should be further investigated.

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Chan, Cheuk-ying, and 陳倬瑩. "Effects of (-)-epigallocatechin gallate in 3T3-L1 adipogenesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B44670679.

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Heath, Victoria J. "Inhibition of adipogenesis by the c-myc oncoprotein." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360306.

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21

Cassidy, Fearon. "The role of Dlk1 in in vivo adipogenesis." Thesis, Queen Mary, University of London, 2018. http://qmro.qmul.ac.uk/xmlui/handle/123456789/46028.

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Misregulation of Dlk1, a paternally expressed imprinted gene, is known to cause adipose phenotypes in both mice and humans. It is now known that the type of fat a person has, the location of and type of expansion are all important factors for the epidemic of obesity-related diseases, yet there is little understanding of the factors that influence which depots expand, and how. This project investigates how Dlk1, expressed primarily during embryogenesis, effects adulthood adiposity, which has shed light on the mechanism by which embryonic insults affect adulthood adipose physiology and resultant metabolic disease. Much previous work has been done on the role of Dlk1 in adipogenesis in vitro, however little is known of its role in this process in vivo. To achieve an in vivo investigation of its role in adipogenesis, adipose tissue has been measured in mice with deleted Dlk1 from embryo through early life and into adulthood. Gross measurement has been supported by mechanistic interrogation of adipose expandability using a triple transgenic adipocyte labelling mouse model, results from which are the most comprehensive to date in a wild type context and reveal insight into the Dlk1 knock-out phenotype. Results indicate a complex and dynamic role of Dlk1 that is interlinked with overall growth in mice. Moreover new evidence is presented here for tissue specific c imprinting of Dlk1 in some adipose cell types with consequential growth and adipose alterations in Dlk1 heterozygote mice that do not follow the expected phenotype of imprinted gene knock-out models.

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22

Christodoulides, Constantinos. "The role of Wnt signalling in human adipogenesis." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613010.

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23

Wu, Yu. "Identification and Functional Characterization of Adipogenesis-related Genes." University of Toledo Health Science Campus / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=mco1229546422.

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24

Adams, Vanessa Lynn. "Adipogenesis in post-weanling pigs fed conjugated linoleic acid." Thesis, Texas A&M University, 2004. http://hdl.handle.net/1969.1/1091.

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The effects of conjugated linoleic acid (CLA) on lipogenesis and preadipocyte proliferation in young pigs were evaluated in two separate experiments. The first compared dietary effects of linoleic acid, beef tallow, and CLA on composition, lipogenesis, and DNA synthesis. Eighteen pigs weaned at 17 d of age were allotted randomly to corn-based diets supplemented with 1.5% corn oil, 1.5% tallow, or 1.5% CLA. The second experiment evaluated the effects of CLA included with diets high in polyunsaturated fat or beef tallow. Twenty-four pigs weaned at 17 d of age were allotted randomly to one of four corn-based diets supplemented with: 15% corn oil, 12% corn oil + 3% CLA, 15% tallow, and 12% tallow + 3% CLA. The piglets in both trials were fed a basal diet for 7 d and their respective diet for 35 d. [U-14C]Glucose incorporation into total lipids was (experiment 1): 10.64, 11.04, 13.64; (experiment 2): 21.15, 17.54, 21.34, and 19.52 nmol/(105 cells per h) for subcutaneous (s.c.) adipose tissue from corn oil, tallow, CLA; corn oil, corn oil + CLA, tallow, and tallow + CLA-fed piglets, respectively. Tritiated thymidine incorporation into DNA was not different in s.c. adipocytes across treatment groups, but was 5,581, 2,794, 6,573, and 3,760 dpm/(105 cells per h) in s.c. stromal vascular cells from corn oil, corn oil + CLA, tallow, and tallow + CLA-fed piglets, respectively (CLA main effect p<0.034). Additionally, there was a greater proportion of s.c. adipocytes in the smaller, 180-pL cell fraction from the corn oil + CLA-fed pigs (p<0.0074). CLA in the diet increased the s.c. adipose tissue concentration of 18:0 and decreased 16:1 and 18:1 (p<0.05), suggesting depression of stearoyl-coenzyme A desaturase (SCD) enzyme activity in the CLA-fed pigs. The concentration of CLA isomers was raised only slightly in s.c. adipose tissue with the addition of CLA to the diets even though the CLA oil contained 62% CLA isomers. No effects on the growth of young pigs were observed. However, CLA caused a more saturated fatty acid composition and may suppress preadipocyte proliferation, apparent SCD activity, and lipid filling of smaller cells.

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25

Abood, Steven. "The Effects of Artemisia Derived Natural Products on Adipogenesis." FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3383.

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For the first time in human history, more people worldwide suffer from obesity than are undernourished. Numerous health complications are associated with obesity including cardiovascular disease, Type 2 Diabetes, cancers of reproductive tissues, stroke, depression, anxiety disorders, and Alzheimer’s disease. A deeper understanding of the anti-adipogenic effects and mechanism of action of sesquiterpene lactones may have pharmacological import in the continuing search for therapeutic modalities to ameliorate the effects of this global obesity epidemic. Dehydroleucodine (DhL), 11,13-dihydro-dehydroleucodine (DH-DhL), and dehydroparashin-B (DhP), sesquiterpene lactones extracted from or derived from compounds extracted from Artemisia douglasiana, were investigated for their anti-adipogenic effects on 3T1-L1 preadipocytes. Dehydroleucodine inhibited the expression of C/EBPa and PPARg, and also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner. Dehydroleucodine arrested the cell cycle at the G0/G1 phase, increased p27 and decreased both cyclins A and D and their partners (e.g., CDK2 and CDK4). Furthermore, DhL downregulated expression of histone demethylase JMJD2 as well as repressed the expression of histone methyltransferase MLL4, which in turn diminished the expression of C/EBPb and PPARg, respectively. 11,13-dihydro-dehydroleucodine blocked the accumulation of lipid droplets and inhibited the expression of PPARγ and C/EBPβ. Collectively, the results indicate that the inhibition of early stage preadipocyte differentiation by DH-DhL may be associated with cell cycle arrest at the G0/G1 phase. Dehydroparashin-B significantly decreased the accumulation of lipid content and downregulated the expression of CEBPβ, PPARγ and CEBPα as well as FAS. Interestingly, the addition of DhP inhibited the number as well as the size of the lipid droplets during the differentiation of 3T3-L1 preadipocytes. Taken together, this data suggests that DhP has an important inhibitory effect on cellular pathways regulating adipocyte differentiation.

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Tsuji, Wakako. "Adipogenesis induced by human adipose tissue-derived stem cells." Kyoto University, 2009. http://hdl.handle.net/2433/126447.

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27

Xaymardan, Munira. "Structural differentiation in cultured endothelial clusters and adipogenic healing." Thesis, The University of Sydney, 2001. http://hdl.handle.net/2123/4715.

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Campos, Carolina Filardi de. "Gene expression and proteomic analysis underlying adipogenesis in livestock." Universidade Federal de Viçosa, 2016. http://www.locus.ufv.br/handle/123456789/9505.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico
Marmoreio ou gordura intramuscular (IMF) é um componente importante da produção animal, já que é um dos principais fatores para a qualidade de carne. IMF é alcançada pela adipogênese, processo de proliferação e diferenciação de pré-adipócitos, e pela lipogênese, com a assimilação subsequente de lipídeos. A compreensão dos eventos que ocorrem durante a diferenciação de pré-adipócitos tem avançado consideravelmente nos últimos anos e baseou-se principalmente no uso de cultura de tecidos. Os modelos animais podem ser utilizados não apenas para a melhor compreensão da deposição de gordura, mas também como modelos para maior compreensão sobre os mecanismos moleculares subjacentes a determinadas condições humanas. Além disso, a diferenciação em adipócitos tem muitas implicações para doenças em humanos. É sabido que esta diferenciação envolve uma cascata transcricional, de modo que o presente estudo proporciona conhecimento sobre genes e fatores de transcrição utilizando a técnica de RT-qPCR, envolvidos na diferenciação de pré-adipócitos em adipócitos maduros comparando duas raças divergentes de suínos. Os resultados mostram que alguns genes são diferencialmente expressos entre a linhagem comercial e a raça Piau. Além disso, um estudo de expressão gênica e um estudo proteômico são fornecidos revelando os efeitos da vitamina A sobre a adipogênese em bovinos, revelando efeito negativo sobre a adipogênese. Assim, destacamos a importância da expressão gênica e dos estudos proteômicos para aumentar a compreensão dos mecanismos moleculares envolvidos na adipogênese.
Marbling or intramuscular fat (IMF) is an important component of livestock production, as it is a major factor in the overall meat quality. IMF is achieved by adipogenesis, the process of proliferation and differentiation of preadipocytes, and lipogenesis, with the subsequent assimilation of lipid. The understanding of events that occur during preadipocyte differentiation has advanced considerably in the last few years and has relied mainly on the use of tissue culture models of adipogenesis. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. Furthermore, adipocyte differentiation has many implications for human disease conditions. It is well known that this differentiation involves a transcriptional cascade, so the present study provided knowledge about genes and transcription factors using RT-qPCR technique, involved in differentiation of preadipocytes into mature adipocytes comparing two divergent pig breeds. The results show us that some genes are differentially expressed between commercial line and Piau breed. Moreover a gene expression and a proteomic study are provided revealing the effects of vitamin A on adipogenesis in cattle, revealing the negative effect on adipogenesis. Thereby, we highlighted the importance of gene expression and proteomic studies to increase the understanding of molecular mechanisms underlying adipogenesis.

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Hadadeh, Ola. "Rôle du système d'activation du plasminogène dans la différenciation des cellules souches embryonnaires de souris." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20718.

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Le système d’activation du plasminogène (AP) comprenant les protéases uPA et tPA, et leur inhibiteur PAI-1, génère une activité protéolytique dans la matrice extracellulaire et contribue au remodelage tissulaire dans une grande variété de processus physiopathologiques, y compris la myogenèse squelettique, et la différenciation adipocytaire.Nous avons évalué son rôle spécifique dans la différenciation des cellules souches embryonnaires (ES) de souris. On a trouvé que les activités d’uPA et de tPA ainsi que les niveaux protéiques de PAI-1 sont maximaux dans les cellules différenciées, contrairement aux cellules ES indifférenciées où ils sont indétectables et augmentent progressivement dès le jour 3 de la différenciation. La différenciation adipocytaire dans le modèle des cellules ES est inhibée par le traitement par l’amiloride, un inhibiteur spécifique de l’uPA. Egalement, les cellules ES surexprimant une forme active du PAI-1 sous le contrôle d’un système d’expression inductible, montrent des capacités adipogéniques réduites après l’induction du gène. Nos résultats démontrent que le contrôle de l’adipogenèse des cellules ES par le système AP correspond à des étapes successives, différentes, depuis les cellules indifférenciées jusqu’aux cellules bien différenciées. De plus, les capacités de la différenciation adipogénique des cellules pluripotentes induites déficientes en PAI-1 sont augmentées par rapport aux cellules contrôles.Similairement, la myogenèse squelettique est réduite par l’inhibition de l’uPA par l’amiloride ou par la surexpression du PAI-1 durant l’étape terminale de la différenciation du jour 7 au jour 24. Cependant, l’interférence avec l’uPA durant les jours 0 à 3 de la différenciation, stimule la formation des myotubes. Les différenciations cardiomyocyotaire, neuronale, endothéliale et du du muscle lisse ne sont pas affectées par le traitement à l’amiloride ou la surexpression du PAI-1.Nos résultats montrent que le système AP est capable de moduler spécifiquement l’adipogenèse et la myogenèse squelettique des cellules ES par des mécanismes moléculaires successifs différents
Regulation of the extracellular matrix (ECM) plays an important functional biological role either in physiological or pathological conditions. The plasminogen activation (PA) system, comprising the uPA and tPA proteases and their inhibitor PAI-1, is one of the main suppliers of extracellular proteolytic activity contributing to tissue remodeling. Although its function in development is well documented, its precise role in mouse embryonic stem cell (ESC) differentiationin vitro is unknown. We found that uPA and tPA activities and PAI-1 protein are very low in undifferentiated ESCs and increase strongly during the differentiation, reaching a maximum in well differentiated cells. Adipocyte formation by ESCs is inhibited by amiloride treatment, a specific uPA inhibitor. Likewise, ESCs expressing ectopic PAI-1 under the control of an inducible expression system, display reduced adipogenic capacities after induction of the gene. Our results demonstrate that the control of ESC adipogenesis by the PA system correspond to different successive steps from undifferentiated to well differentiated ESCs. Furthermore, the adipogenic differentiation capacities of PAI-1-/- induced pluripotent stem cells (iPSCs) are augmented as compared to wt iPSCs. Similarly, skeletal myogenesis is decreased by uPA inhibition or PAI-1 overexpression during the terminal step of differentiation. However, interfering with uPA during days 0 to 3 of the differentiation process augments ESC myotube formation. Neither neurogenesis, cardiomyogenesis, endothelial cell nor smooth muscle formation are affected by amiloride or PAI-1 induction. Our results show that the PA system is capable to specifically modulate adipogenesis and skeletal myogenesis of ESCs by successive different molecular mechanisms

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Moratal, Claudine. "Les progéniteurs fibro-adipogéniques des muscles squelettiques humains sains et dystrophiques : caractérisation et interactions avec les progéniteurs myogéniques et les macrophages." Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4128/document.

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La régénération musculaire implique des interactions fonctionnelles entre différents types de cellules mononucléées. Parmi elles, citons les progéniteurs myogéniques (MPs), qui fusionnent pour générer de nouvelles myofibres en réponse à une blessure, et les cellules immunitaires qui envahissent les muscles endommagés. Des dépôts transitoires fibrotiques et d’adipocytes sont observés dans les muscles en régénération qui cependant persistent dans la dystrophie musculaire de Duchenne (DMD) et au cours du vieillissement. Nous avons démontré que les progéniteurs fibro-adipogéniques (FAPs) exprimant le marqueur de surface PDGFRα, contribueraient au développement des dépôts non myogéniques dans les muscles sains. En effet, ces progéniteurs se différencient en adipocytes blancs fonctionnels, bien qu’étant insensibles à l’insuline, et génèrent des myofibroblastes. Quant à la fibrose des muscles DMD, elle se formerait à partir de la différenciation à la fois des MPs et des FAPs. Dans les muscles sains, les FAPs stimulent la myogenèse des MPs au cours de la régénération, alors que les myotubes et les macrophages pro-inflammatoires inhibent l’adipogenèse et la fibrogenèse des FAPs. Pour les progéniteurs âgés ou dystrophiques, les interactions cellulaires entre les FAPs et les MPs sont perturbées. De manière intéressante, la régulation des FAPs DMD ou âgés peut être restaurée en remplaçant les MPs DMD ou âgés par des MPs jeunes et sains. Nos résultats montrent que les muscles humains contiennent des progéniteurs fibro-adipogéniques qui jouent un rôle central dans la régulation de l’homéostasie musculaire en interagissant avec les progéniteurs myogéniques et les macrophages
Muscle regeneration involves functional interactions between different types of mononuclear cells including myogenic progenitors (MPs) and macrophages. Following injury, damaged muscles are invaded by immune cells and MPs fuse to generate new myofibres. Transient fibrotic and adipocyte deposits are observed in regenerating muscles, which however persist in Duchenne muscular dystrophy (DMD) and during aging. We demonstrated that fibro-adipogenic progenitors (FAPs) expressing the PDGFRα surface marker would contribute to the development of non-myogenic deposits in healthy muscles. Indeed, these progenitors differentiate into functional white adipocytes that have the feature to be insulino-resistant, and give rise to myofibroblastes. Intramuscular fibrosis in DMD patients could be formed from both FAPs and MPs differentiation. In healthy muscles, FAPs stimulate myogenesis of MPs during regeneration, while myotubes and pro-inflammatory macrophages inhibit the adipogenesis and fibrogenesis of FAPs. Cellular interactions between FAPs and MPs are disrupted for DMD or aged progenitors. Interestingly, they are restored if aged or DMD FAPs are replaced by healthy and young MPs. Our results show that the human muscles contain fibro-adipogenic progenitors that play a crucial role in the control of muscle homeostasis by interacting with myogenic progenitors and macrophages

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Joe, Aaron Wai Bun. "Identification, isolation and characterization of murine adult adipogenic progenitor cells." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/22316.

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White adipose tissue, or fat, is a complex endocrine tissue important for energy storage and metabolism, and has significant effects on various physiological phenomena, including growth, behaviour, reproduction and immune-modulation. It has been proposed that fat cells, or adipocytes, arise from connective tissue cells that fill with lipid; however, mounting evidence suggests that adipocytes represent a distinct lineage with its own cellular origins. Yet very little is known about the cells that give rise to new adipocytes. Here, my colleagues and I developed a strategy to isolate purified populations of adipogenic progenitor (AP) cells from subcutaneous fat, visceral fat and skeletal muscle, using fluorescence-activated cell sorting. These cells are capable of robust adipogenic differentiation, even at the single cell level. We confirmed their commitment to the adipogenic lineage using a variety of assays, and reveal that they are lineage-restricted cells, incapable of osteogenic, chondrogenic or myogenic differentiation. Thus, we have developed an enabling technology to allow interrogation of the adipocyte lineage among different tissues and fat depots, during different physiological, pathological or developmental stages. Recent evidence suggests that fat depots with a greater ability to generate new adipocytes are associated with lower metabolic risk. Using our isolation strategy, we confirmed that metabolically healthier depots are associated with greater AP abundance and activity, uncovering a link between stem cell biology and metabolic disease. However, adipocyte production in non-adipose tissues, such as skeletal muscle and bone marrow, is associated with chronic disease and aging. To explore possible reasons for this dichotomy, we examined the role of APs in a model of skeletal muscle injury. Our results suggest that APs expand after damage to assist in muscle regeneration by establishing a pro-myogenic niche, ascribing to them a novel function that is independent of adipogenesis. Together, our strategy to interrogate the adipogenic lineage has allowed us to formulate new hypotheses to explain adipose and skeletal muscle physiology. This technology forms the basis for future work that will to allow us to understand how new adipocytes are formed, and perhaps permit the manipulation of adipogenic progenitors for therapeutic benefit.

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Al-Jabir, M. J. M. H. "Regulation of adipogenesis and inflammation : role(s) of adipose microRNAs." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1473942/.

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Background: Obesity is associated with elevated risk of premature death and a range of co-morbidities. It is multifactorial and heterogeneous in origin, and, stratification of this disease, depending on the range of associated pathogenicities could help identify mediators and in the design of targeted therapies. Recent research has focused on microRNA (miRs) as potential biomarkers of cardiovascular risk, as well as their role as causative agents in the obesity associated pathologies. Aims of the project were to: 1. Stratify obese subjects depending on systemic biomarkers of insulin resistance and inflammation. 2. Identify and validate specific miRs associated with these phenotypes. 3. Confirm and validate, in the whole transcriptome, targets for the specific miRs to assign functionality. Methods: Non-diabetic, morbidly obese subjects of Arab origin were studied. Blood and adipose tissue samples were obtained before and after weight loss, along with anthropometric data. Glucose and lipids levels were determined by conventional methods. Insulin and adipokine concentrations were assayed by commercially available 2-site ELISA (R & D Systems, Oxon, UK). The population was dichotomised according to their serum insulin levels: Metabolically Healthy Obese (MHO) insulin < 6.5 miU/ml; Patholigcally Obese (PO) insulin > 7.0 miU/ml. Total RNA, including miR, was extracted from peripheral blood cells, whole adipose tissue, the stromal vascular fraction and adipocytes of the abdominal subcutaneous and omental adipose tissues. miR expression was assessed using an inflammatory pathway specific array (Qiagen), and by small RNA sequencing (Ion Torrent). mRNA expression was assessed by whole transcriptome analysis (Ion Proton) and validated by PCR based microarrays (SurePrint G3 Human Gene Expression). Results: PO, matched for age and BMI, had significantly higher serum insulin levels and HOMA index of IR, compared to MHO. They also had higher leptin, a marker of fat mass and adipocyte hypertrophy, and lower adiponectin, an endogenous insulin sensitizer. However, blood pressure, lipids and inflammatory markers, such as IL-6, MCP-1 and CRP were not significantly different between the groups. Three miRs were significantly down-regulated in the PO; miR-29, miR-144 and miR- 374, and associated with inflammation, along with miR-122, miR-302, miR-200, which were associated with hyperinsulinaemia and insulin resistance. Many of their targets, especially those of miR-29, showed elevated expression in the PO. Following surgical weight loss there was a significant reduction in insulin which correlated with an increase in the levels of expression of nine miRs; miR-9, miR-200c, miR-141, miR-124, miR- 376c, miR-302, while one was downregulated, miR-26b. Whole transcriptome analysis of mRNA in blood and adipose tissue revealed modulation of several genes in the cardiometabolic pathways in the PO compared to MHO, along with genes leading to increased fibrosis. Conclusions: Significant differences in the expression of specific miR species occured along with insulin resistance and inflammation in PO compared to MHO. The target genes of these miRs, especially miR-29, miR-144 and miR-122, suggested fibrosis, in the presence of IR and inflammation, as a major lesion in these patients. Functional studies to explore the role of these miRs in fibrosis may offer new insights on putative therapeutic targets for this group of patients.

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Tam, Joshua. "Adipogenesis and angiogenesis : roles in tissue engineering and glucose metabolism." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/54590.

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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 118-127).
Adipose tissue serves two main functions in the body: (1) it is the body's primary energy depot; and (2) it also serves as an important endocrine organ, producing and secreting various enzymes, growth factors, cytokines, and hormones. Both of these functions require ample access to circulating blood. Many aspects of angiogenesis during adipose tissue expansion remain poorly understood. Adipocytes produce a large variety of molecules involved in angiogenesis, and obesity is associated with elevated circulating levels of Vascular Endothelial Growth Factor (VEGF). Our lab has previously shown that angiogenesis and adipogenesis are mutually dependent via a VEGF receptor 2 (VEGFR2)-mediated mechanism. Since then several other studies have reinforced a role for the VEGF-VEGFR system in energy metabolism. For example, genetically obese mice treated with anti-VEGF antibody had lower fat pad weights, but the VEGF receptor responsible for this observation is not known. There is also disagreement on the cell type(s) responsible for fat tissue's angiogenic capability, with some studies supporting a dominant role for adipocytes, while others attribute most of the angiogenic capacity to the adipose tissue stromal cells (ASC). This thesis project aimed to fill some of these gaps by examining the angiogenic capacity of adipose tissue relative to other tissues, the effects of VEGFR-1 and R-2 blockade in mouse models of adipogenesis and diet-induced obesity, the respective angiogenic capabilities of adipocytes and ASC, and the possibility of harnessing the angiogenic potential of adipose tissue for vascular tissue engineering.
(cont.) In addition, a physiologically-based mathematical model was developed to simulate the regulatory effects of the leptin pathway on murine energy homeostasis.
by Joshua Tam.
Ph.D.

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34

Lee, Aishlin Elizabeth. "Selenium Treatment Promotes Adipogenesis in Chicken Embryonic Fibroblasts In Vitro." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1367416159.

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35

Cawthorn, W. P. "Molecular mechanisms of anti-adipogenesis by tumour necrosis factor-alpha." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597378.

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In this thesis, a candidate approach was taken to analyse the temporal characteristics of gene expression during TNF-α induced anti-adipogenesis. This suggested that TNF-α might activate Wnt/β-catenin signalling during anti-adipogenesis. Further investigations revealed stabilisation of β-catenin, enhanced TCF7L2 promoter activity and enhanced expression of Wnt/TCF7L2 target genes. The requirement of Wnt/β-catenin signalling for this process was investigated in preadipocytes with either stable knockdown of β-catenin or overexpression of a dominant-negative mutant of the transcription factor TCF7L2. Knockdown of β-catenin attenuated anti-adipogenesis and enhanced apoptosis by TNF-α, whereas overexpression of dnTCF7L2 prevented TNF-α-induced anti-adipogenesis without affecting cytotoxicity. The studies presented in this thesis also identify the serine kinase IKKi as a negative regulator of adipogenesis. IKKi expression was downregulated during adipogenesis but elevated during early TNF-α-induced anti-adipogenesis. Forced expression of IKKi attenuated adipogenesis, whereas stable knockdown of IKKi enhanced adipogenesis. TNF-α also regulated IKKi in mature adipocytes, and knockdown of IKKi in these cells blunted both the suppression of adipocyte genes and the induction of insulin resistance by TNF-α. Importantly, IKKi expression was found to be upregulated in the adipose tissue of obese and insulin-resistant mice and humans, conditions where TNF-α levels are known to be elevated and where adipogenesis may be impaired. In conclusion, the studies have identified two novel mechanisms by which TNF-α can inhibit adipogenesis: via a β-catenin/TCF7L2-dependent pathway and via induction of IKKi. These novel mechanisms of TNF-α action may impact on other aspects of cell fate determination, such as cell proliferation and survival.

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AGUIARI, Paola. "High Glucose Induces Adipogenic Differentiation of Muscle-Derived Stem Cells." Doctoral thesis, Università degli studi di Ferrara, 2009. http://hdl.handle.net/11392/2388681.

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Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ROS production and PKCβ activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKCβ siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously uncharacterized differentiation route triggered by high glucose that drives not only resident stem cells of the adipose tissue but also uncommitted precursors present in muscle cells to form adipose depots. This process may represent a feed‐forward cycle between the regional increase in adiposity and insulin resistance that plays a key role in the pathogenesis of diabetes mellitus.

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Batrakou, Dzmitry G. "Nuclear envelope transmembrane proteins in differentiation systems." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/9981.

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Historically, our perception of the nuclear envelope has evolved from a simple barrier isolating the genome from the rest of a cell to a complex system that regulates functions including transcription, splicing, DNA replication and repair and development. Several recent proteomic studies uncovered a great variety of nuclear envelope transmembrane proteins (NETs). Diseases associated with several nuclear envelope proteins, mostly NETs, affect many tissues e.g. muscle, adipose tissue, skin, bones. Many NETs of the inner nuclear membrane have been shown to interact with chromatin, suggesting that their influencing gene expression might explain NET roles in disease. This work is focused on finding novel interactions of NETs with chromatin. First, SUN2 post-translational modifications were analysed and the effect of phosphomimetic and phospho-null mutants on heterochromatin and the cytoskeleton was tested by overexpression. However, no obvious changes were found. Second, several tissue-preferential NETs were tested in an adipocyte differentiation system. NET29 changed chromosome 6 position in pre-adipocytes. This matched changes in chromosome positioning that occur during adipocyte differentiation when NET29 is normally induced. Post-translational modifications of NET29 are likely to play a vital role in this process because a phospho-null mutant dominantly blocked chromosome repositioning. The effect of over-expression and down-regulation of NET29 on transcription was tested and results suggest that NET29 negatively regulates expression of myogenic genes during adipogenesis. This thesis is split into six chapters. Chapter I is an overview of the nuclear envelope, adipogenesis and chromatin remodelling, Chapter II is a detailed description of methods used in this study. Chapter III focuses on post-translational modifications of SUN2, as well as trials to identify novel partners of SUN2. Chapter IV and V deal with a novel nuclear envelope transmembrane protein and its role in adipogenesis. Finally, the last chapter includes a discussion and recommended future directions.

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Peshdary, Vian. "Effect of Glucose on Human Adipogenesis and its Regulation by Macrophages." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35051.

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Adipose tissue expands via differentiation of preadipocytes into adipocytes (adipogenesis) and/or hypertrophy of existing adipocytes. A low adipogenic capacity promotes adipocyte hypertrophy, causing inflammatory macrophage accumulation and insulin resistance. Macrophage-conditioned medium (MacCM) inhibits adipogenesis and promotes adipocyte inflammation, but it is unknown if these effects are altered by high glucose (HG) versus normal glucose (NG) concentrations. The effect of HG on adipogenesis was assessed. Human subcutaneous abdominal preadipocytes were induced to differentiate in HG or NG conditions. HG did not affect adipogenesis. HG increased ChREBP-β mRNA and protein levels, and increased GLUT4 mRNA, in differentiated adipocytes. It did not change mRNA levels of ACC, SCD, and FAS. The increase in ChREBP-β mRNA was positively correlated with HG-induced increase in GLUT4 mRNA. The effect of HG-MacCM versus NG-MacCM on human adipogenesis and adipocyte inflammation was compared. Human monocyte-derived macrophages (MDM) were placed in NG or HG glucose for 24 hours to generate MacCM. HG-MacCM, but not NG-MacCM inhibited triacylglycerol accumulation and protein expression of PPARγ during human adipogenesis. Preadipocytes differentiated in HG-MacCM displayed a more pro-inflammatory phenotype, as assessed by increased MCP-1 and IL-6 and reduced adiponectin mRNA expression. HG increased phosphorylation of IKK-β and decreased protein expression of IκBα in MDMs. In addition, HG reduced protein expression of PPARγ in MDMs. The pro-inflammatory effect of HG-MacCM on MCP-1 expression in adipocytes was partially inhibited when MDMs were treated with sc-514 (IKKβ inhibitor). My data demonstrate that HG-induced expression of ChREBP-β in adipocytes may be associated with increased GLUT4 mRNA. The anti-adipogenic and pro-inflammatory effects of HG-MacCM are more potent than NG-MacCM. This suggests the possibility that adipose tissue cellular remodeling in vivo may be altered with hyperglycemia.

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Abaiian, Kayvan Jasper. "Regulation of aortic carboxypeptidase-like protein (ACLP) during 3T3-L1 adipogenesis." Thesis, University of Ottawa (Canada), 2001. http://hdl.handle.net/10393/9355.

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The 175 kD aortic carboxypeptidase-like protein (ACLP), suggested to be involved in smooth vascular muscle cell differentiation, has been shown to be expressed in 3T3-L1 preadipocytes. In this study we demonstrate that ACLP protein expression is transiently but significantly down-regulated by day 2 of an 8-day 3T3-L1 differentiation. ACLP protein down-regulation correlates with increases in cell number, suggesting a potential link between ACLP and clonal expansion. The transient modulation of ACLP is shown to be partly due to transcriptional regulation. Analysis of the individual components of differentiation cocktail indicate that all components are necessary to induce maximal ACLP downregulation and, as such, this event is differentiation-dependent. Although ACLP overexpression had no apparent effect on adipogenesis, its pattern of expression, unique to post-mitotic proliferation, indicates a potential role for ACLP in adipose tissue development and warrants further investigation to elucidate its function during preadipocyte differentiation.

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Muise, Aleixo Michael. "Adipocyte enhancer binding protein (AEBP1), a multifunctional protein involved in adipogenesis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq24756.pdf.

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Tam, Ka-shing, and 譚家承. "Effects of bitter melon extracts on adipogenesis of 3T3-L1 adipocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42182037.

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Pell, Vidal Núria. "CPEB4-Driven adipocyte reprogramming is required for adipogenesis and pathological inflammation." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/671750.

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Obesity is reaching pandemic dimensions and is an established instigator of many diseases, such as non alcoholic fatty liver disease, the most prevalent liver disease worldwide. Most studies in this regard have been focused on obesity-related disturbances taking place within the liver altough the implications of obesity on extrahepatic abdominal organs are of major relevance to get the whole picture of the disease. Here, we show that the RNA-binding protein CPEB4 is highly expressed in visceral fat during obesity and obesity associated liver disease, where it orchestrates a posttranscriptional reprogramming necessary for development and aggravation of diet-induced obesity. CPEB4 simultaneously regulates adipocyte differentiation and expansion, and the adipocyte-macrophage crosstalk. Consequently, CPEB4 depletion prevents the upregulation of adipocyte-related pathways and adipogenesis, and promotes an anti-inflammatory phenotype in visceral adipose tissue. These findings identify CPEB4 as an appealing therapeutic target for obesity.

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43

Yamada, Tomoya. "Studies on the expression of adipogenic transcription factors in beef cattle." Kyoto University, 2011. http://hdl.handle.net/2433/135406.

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Noguchi, Michio. "Genetic and pharmacological inhibition of Rho-associated kinase 2 enhances adipogenesis." Kyoto University, 2008. http://hdl.handle.net/2433/135793.

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45

Tam, Ka-shing. "Effects of bitter melon extracts on adipogenesis of 3T3-L1 adipocytes." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42182037.

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46

Guth, Sinja Viktoria [Verfasser]. "Untersuchungen zur Differenzierung equiner, adipogener, mesenchymaler Stammzellen zu Tenozyten / Sinja Viktoria Guth." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/1065251297/34.

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Moseti, Dorothy. "25 Hydroxycholesterol inhibits adipogenesis and expression of adipogenic transcripts in C3H10T1/2 mouse stem cells independent of hedgehog signalling mechanism." 2015. http://hdl.handle.net/1993/30577.

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This study was conducted to assess the effects of specific oxysterols on the adipogenic differentiation and expression of adipogenic transcripts in C3H10T1/2 mouse stem cells. In the first study, four oxysterols namely; 20S, 22R, 22S and 25 hydroxycholesterol (25-HC) were tested to determine which one best inhibits adipogenesis in C3H10T1/2 mouse stem cells. Adipogenic differentiation was induced using an adipogenic media (DMITro) consisting of dexamethasone (DEX), 3-isobutyl-1-methyl-xanthine (IBMX), insulin and troglitazone (Tro). Inhibition of adipogenesis was assessed by treatment of cells with DMITro+20S, 22R, 22S or 25-HC for six days. Oil red O pictures and gene expression analysis showed that 25-HC was more effective in inhibiting the expression of adipogenic genes compared to the other oxysterols. Further investigation of the mechanisms of action of 25-HC showed that the inhibitory effects of 25-HC on adipogenesis are not mediated by hedgehog signalling.
October 2015

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48

Deuschl, Jana Daniela. "Der Einfluss des Transkriptionsfaktors Runx2 auf osteogene und adipogene Differenzierungsmarker, insbesondere auf PPARγ." Doctoral thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0022-5DE8-D.

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Mesenchymale Stammzellen können sich durch den Einfluss verschiedener Transkriptionsfaktor zu Osteoblasten, Adipozyten, Chondrozyten oder Myoblasten differenzieren. Während sie sich unter Runx2-Einfluss entlang der osteoblastären Linie differenzieren, entwickeln sie sich bei vorliegendem PPARγ entlang des adipogenen Differenzierungswegs. Das Gleichgewicht zwischen beiden Faktoren und ihr Zusammenspiel stellen einen wichtigen Bereich in der Osteoporoseforschung dar. In dieser Dissertation wurde durch Runx2-Suppression bzw. Runx2-Überexpression die Rolle dieses Faktors in pHOB und SCP1-Zellen erfasst und die Interaktion zwischen Runx2 und PPARγ untersucht. Der Runx2-Knockdown’ erfolgte mittels RNA-Interferenz, die Runx2-Überexpression durch ein Runx2 exprimierendes Plasmid. In RT-PCRs wurden mRNA-Messungen durchgeführt. Die Proteinbestimmung erfolgte im ‚Westernblot’. Der funktionelle Einfluss der Runx2-Überexpression auf die PPARγ-Transkription wurde durch Kotransfektion des an Luziferase gekoppelten PPARg-Promotorgens erfasst. Die funktionelle Aktivität des PPARg-Proteins wurde durch die Transfektion des an Luziferase gekoppelten PPRE-Gens gemessen. Promotoraktivität und Funktionalität der Proteine wurden in Luziferase-Reportergenassays erfasst. Unter basalen Kulturbedingungen differenzierten sich pHOB osteogen. Durch zweimalige siRunx2-Transfektion gelang auf mRNA-Ebene eine suffiziente Runx2-Suppression über 29 Tage auf durchschnittlich 10,1%. Neben einer Steigerung der PPARγ-mRNA nach sieben Tagen konnte darunter auch eine Suppression der osteogenen Differenzierungsmarker OC und AP beobachtet werden. Ein ‚Rescue’ der supprimierten Runx2-Genexpression konnte durch osteogene Stimulation nicht erreicht werden. In den Runx2-/PPARγ-Interaktionsversuchen wurden SCP1-Zellen adipogen stimuliert, um die PPARγ2-mRNA und PPARγ-Promotoraktivität zu erhöhen. Darunter konnte ebenfalls eine gesteigerte Funktionalität des PPARγ-Proteins beobachtet werden. Durch Runx2-Überexpression wurde in SCP1-Zellen die PPARγ-Promotoraktivität und somit der Beginn der mRNA-Synthese gehemmt. Die PPARγ2-mRNA hingegen blieb unbeeinflusst. Die zentrale Rolle des Runx2 in der osteogenen Differenzierung scheint durch den Einfluss auf die osteogenen Marker OC und AP in pHOB bestätigt zu werden. Auch der Einfluss auf die adipogene Differenzierung erfolgt über Runx2. Im Rahmen dieser Dissertation konnte erstmalig die Hemmung des PPARγ-Promotors durch Runx2 beschrieben werden. Hierdurch werden die PPARγ-Transkription und somit voraussichtlich die Interaktion zwischen Adipogenese und Osteogenese beeinflusst.

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Iannantuono, Nicholas. "Régulation du facteur de transcription FOXK1 par O-GlcNAcylation : implications dans la différenciation adipocytaire." Thèse, 2015. http://hdl.handle.net/1866/13646.

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Les modifications post-traductionnelles telles que la phosphorylation, l’OGlcNAcylation et l’ubiquitination jouent des rôles critiques dans la coordination des fonctions protéiques et par conséquent influencent grandement de nombreux processus cellulaires. Il est à noter que ces modifications sont hautement dynamiques et finement regulées. Par exemple, l’ubiquitination peut être réversible via l’action des déubiquitinases comme le suppresseur de tumeurs BAP1. Parmis les gènes codant pour les déubiquitinases, BAP1 est la plus souvent mutée dans le cancer. Des études récentes ont démontré l’importance des dynamiques de modifications post-traductionnelles dans la régulation du complexe BAP1. En plus, BAP1 forme un complexe multi-protéiques contenant plusieurs régulateurs transcriptionnels comme la protéine polycomb OGT et les facteurs de transcription FOXK1 et FOXK2. OGT est une enzyme unique qui catalyze l’ajout d’un groupement O-GlcNAc sur ses substrats afin d’en moduler l’activité enzymatique, les interactions protéines-protéines et leur localisation cellulaire. Cette modification est aussi liée au métabolisme puisque son substrat donneur, l’UDP-GlcNAc, est dérivé de la voie biosynthétique des hexosamines. Parallèlement, FOXK1/2 ont aussi été démontrés comme étant critiques à des processus métaboliques telles que la myogenèse et l’autophagie. Lors de nos études, nous avons identifié FOXK1 comme un nouveau substrat d’OGT. De plus, les niveaux d’O-GlcNAcylation de FOXK1 fluctuent lors de l’entrée/sortie du cycle cellulaire. En outre, nous avons identifié l’importance de FOXK1 dans l’adipogenèse et observé que l’interaction FOXK1/BAP1 est affectée par le métabolisme cellulaire. En résumé, nos études ont révélé l’importance d’OGT dans la régulation de certaines composantes du complexe BAP1, ce qui aidera à la compréhension de l’effet suppresseur de tumeur de BAP1 ainsi que son mécanisme d'action dans différents processus tel que le remodelage de la chromatine.
Post-translational modifications such as phosphorylation, O-GlcNAcylation and ubiquitination play critical roles in coordinating protein function and are therefore involved in diverse cellular processes. Of relevance here, ubiquitination may be removed by deubiquitinases such as the tumour suppressor BAP1, which represents the most mutated deubiquitinase gene in the human genome. Recent studies have revealed that important and dynamic post-translational modifications regulate several functions of the BAP1 complex. Indeed, BAP1 has been shown to form a multi-protein complex with several transcriptional regulators including the polycomb group protein OGT and the transcription factors FOXK1 and FOXK2. OGT is a unique enzyme that catalyzes the addition of an O-GlcNAc moiety to target proteins, which impacts protein function including enzymatic activity, protein-protein interactions and subcellular localization. This modification is also highly linked to cellular metabolism, as the donor substrate for the reaction, UDP-GlcNAc, is derived from the hexosamine biosynthesis pathway. Similarly, FOXK1 and FOXK2 have been shown to be implicated in metabolic processes such as myogenesis and autophagy. During our studies, we identified FOXK1 but not FOXK2 as a novel substrate of OGT. Further, we found that this OGlcNAcylation is modulated during the entry/exit of cell cycle. We also found that FOXK1 is critical for adipogenesis and that the interaction between FOXK1/BAP1 is compromised during nutrient starvation. Thus, our studies have revealed that OGT selectively modulates and regulates components of the BAP1 complex which may impact different cellular processes, notably chromatin remodelling and could help understanding how BAP1 acts as a tumor suppressor.

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Labrecque, Benoît. "Identification de gènes impliqués dans le développement du tissu adipeux et caractérisation de PON3 et de son impact sur divers paramètres de production chez le porc." Thèse, 2008. http://hdl.handle.net/1866/6403.

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Dissertations / Theses on the topic 'Adipogensi'

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