Дисертації з теми "Leptin signaling"
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Buo, Carrie L. "ON LEPTIN AND LEARNING: INVESTIGATING THE INTERACTION OF LEPTINA SIGNALING AND LEARNING IN ZEBRAFISH." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron162428966535721.
Повний текст джерелаVauthier, Virginie. "Etude des Endospanines, une nouvelle famille de protéines régulatrices des fonctions du récepteur de la leptine." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T097.
Повний текст джерелаObesity is one of the greatest current public health challenges, not only in industrialized countries but also in developing countries. The hypothalamic arcuate nucleus (ARC) is a major integration centre for energy and glucose homeostasis that responds to peripheral hormones such as leptin. Resistance to leptin in the ARC is an important component of obesity development and its prevention or reversal represents a major therapeutic goal. Our laboratory recently described endospanin 1 as a negative regulator of the leptin receptor (OB-R) that by interacting with OB-R retains the receptor inside the cell. Interestingly, both proteins are expressed from the same promoter. Silencing of endospanin 1 in the ARC prevented the development of diet-induced obesity demonstrating the importance of this protein on OB-R in vivo function.Based on these encouraging findings the first aim of this thesis was to extend our understanding of the in vitro and in vivo role of endospanin 1 and its homologue, endospanin 2, on OB-R function. The second aim consisted in the identification of chemical compounds able to sensitize the leptin response in obese patients. We show here that endospanin 1 is up-regulated in the ARC of obese mice suggesting a potential contribution of this protein to the development of leptin resistance. Its silencing in the ARC of naïve and obese mice reverses obesity development and impairs pancreatic insulin secretion. This dual effect correlates with the differential effect of endospanin 1 on OB-R signaling, inhibition of the STAT3 pathway and activation of the AKT pathway. Intriguingly, endospanin 2, the second member of the endospanin family, promotes efficient STAT3 activation suggesting differential roles of both endospanins on OB-R function.We characterized an obese patient carrying a homozygous deletion in the chromosomal 1p31.3 region coding for endospanin 1. This is the first report defining the consequences of endospanin 1-deficiency in humans. Our data suggest that endospanin 1 has no major OB-R-independent functions thus defining endospanin 1 as an attractive and highly specific therapeutic target for the improvement of impaired leptin signaling.In the last part of the thesis two screening assays were developed to identify compounds that either activate OB-R or promote its cell surface expression. Primary screens were successfully performed for both assays and positive hits identified. Validated hits might be useful to resensitize the impaired leptin response in obese patients
Dupuis, Lisa. "Molecular mechanisms of leptin receptor signaling in ovarian granulosa cells." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114600.
Повний текст джерелаLes écarts extrêmes de poids par rapport à ce qui est considéré comme un poids normal, telles que l'anorexie et l'obésité, sont liées à des problèmes de la fonction reproductrice chez la femme. Découverte en 1994, la leptine est une hormone sécrétée par le tissu adipeux dans le but d'informer l'hypothalamus sur l'état de satiété de l'organisme. La libération de leptine est directement proportionnelle à la quantité de tissu adipeux et la présence de l'hormone et de son récepteur (Lepr) a été montrée dans différents tissus incluant les cellules de la granulosa des ovaires. Par conséquent, la leptine, via son récepteur, joue un rôle dans la fonction reproductrice de la femme. De nombreuses études ont étudié les effets de Lepr dans les cellules de la granulosa et dans l'ovaire, mais elles ont toutes été réalisées in vitro et les résultats sont contradictoires. Nous présentons ici la première étude in vivo dans le but d'examiner le rôle de Lepr dans les cellules de la granulosa pendant le développement folliculaire et l'ovulation. Des souris immature produisant un grand nombre d'ovocytes ont été utilisées dans toutes nos expériences et les cellules de la granulosa ont été collectées par ponction folliculaire. Les profils d'expression des isoformes de Lepr (LeprA et LeprB) durant les développements folliculaire et lutéal ont été d'abord déterminés, ainsi que ceux des molécules de la voie de signalisation de la leptine et leurs cibles. Les facteurs de transcription régulant potentiellement l'expression de Lepr dans les cellules de la granulosa ont aussi été analysés. Pour évaluer la réponse des cellules de la granulosa à la leptine in vivo, l'hormone leptine a été administrée à différents moments des développements folliculaire et lutéal. Enfin, le récepteur Lepr a été bloqué grâce à l'utilisation d'un antagoniste de Lepr (SMLA) et les effets de ce blocage sur l'ovulation ont été analysés. L'expression de LeprA et LeprB ont augmenté 4h après administration d'hCG, LeprA étant l'isoforme la plus abondante et présentant une expression 23 fois plus importante de 0 à 4h post-hCG. L'expression de la leptine a augmenté durant le même temps ainsi que celle des molécules de la voie de signalisation de Lepr, Stat3 et Socs3, juste après l'induction de Lepr, respectivement 7h et 12h post-hCG. Cebpb, qui a été induit 1h post-hCG, a été identifié comme étant associé au promoteur de Lepr et donc comme étant un régulateur de l'expression de Lepr. Les données concernant la protéine Egr1 et ses ARNm suggèrent qu'il peut s'agir d'un autre potentiel facteur de transcription régulant l'expression de Lepr, notamment en raison d'une augmentation de son expression 1h post-hCG, juste avant l'augmentation de l'expression de Lepr. Les profils d'ARNm des gènes examinés ont donc fourni la preuve du rôle de Lepr durant la période périovulatoire. Ceci a été ensuite confirmé par l'augmentation de la réponse des cellules de la granulosa in vivo suite à une dose physiologique de leptine 6h post-hCG , mise en évidence par la phosphorylation des protéines Mapk et Stat3. Le traitement avec la leptine a aussi accru l'expression des gènes impliqués dans l'ovulation Adamts1, Pdcd1 et Egr1. Le blocage de l'action de Lepr a réduit le taux d'ovulation de 60% chez les animaux traités avec SMLA. Cette réduction apparaît être due, au moins en partie, à la dérégulation de l'expression des gènes de Adamts10, Adamts19, Has2, Areg, Ptx3, et Foxo1. En conclusion, les résultats de cette étude éclairent les mécanismes moléculaires de l'induction du récepteur Lepr ainsi que de la voie de signalisation qui lui est associée dans les cellules de la granulosa. Pour finir, cette étude fournit des preuves concernant le rôle positif joué par la leptine et Lepr durant l'ovulation, ce qui est essentiel pour optimiser la fertilité de la femme.
Ramirez, Oscar. "Implication for the role leptin-induced signaling as a negative regulator of dendritic cell function." To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2009. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Повний текст джерелаVaughan, Tamisha Y. "Novel Mechanisms Underlying the Inflammatory Effects of Leptin and Low Dose Endotoxin." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/28013.
Повний текст джерелаPh. D.
Dalman, Mark R. "Characterization of Leptin Signaling in the Developing Zebrafish (Danio rerio) Using Molecular, Physiological, and Bioinformatic Approaches." University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1418039468.
Повний текст джерелаKuri, Rodríguez Paola Sofía [Verfasser], and Maria [Akademischer Betreuer] Leptin. "Teleost fish models for the in vivo study of inflammasome signaling / Paola Sofía Kuri Rodríguez ; Betreuer: Maria Leptin." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1178008215/34.
Повний текст джерелаSchumacher, Michael Andrew. "Placental Signaling Mechanisms Linking Maternal Obesity, High-Fat Diet, and Adiponectin Levels During Pregnancy to Fetal Overgrowth." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1243013168.
Повний текст джерелаFaßhauer, Martin [Verfasser], Christoph [Akademischer Betreuer] Buettner, Dirk [Akademischer Betreuer] Raddatz, and Blanche [Akademischer Betreuer] Schwappach. "The role of leptin and insulin signaling in the hypothalamic control of liver metabolism / Martin Faßhauer. Gutachter: Dirk Raddatz ; Blanche Schwappach. Betreuer: Christoph Buettner." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1044870028/34.
Повний текст джерелаRonveaux, Charlotte. "Mécanisme des hormones anorexigènes régulant la prise alimentaire au niveau du nerf vague." Thesis, Paris, AgroParisTech, 2015. http://www.theses.fr/2015AGPT0002/document.
Повний текст джерелаAs the initial interface for nutrient sensing, digestion and absorption, the gastrointestinal (GI) tract plays a critical role in the regulation of energy homeostasis. Information that arises from the GI tract is key to normal physiological responses controlling gut function and regulating food intake. Vagal afferent neurons (VAN) are a major pathway by which information about ingested nutrients reaches the central nervous system to influence GI function and food intake behavior. VAN express receptors for many of the regulatory peptides released from the gut that are involved in regulation of food intake and body weight. This dissertation addresses the role of two gut peptides, leptin and glucagon-like peptide-1, acting at the level of VAN, to inhibit food intake. First, the mechanism of action of glucagon-like peptide-1 (GLP-1) on VAN is addressed. GLP-1-induced satiation requires a postprandial state; the data support that feeding changes the localization of GLP-1Rs from the cytoplasm to the neuronal cell membrane. Further, ghrelin and its receptor GHSR1 expressed by VAN is involved in regulating GLP-1 receptor translocation. Second, the importance of leptin receptor expression by VAN in the development of hyperphagia and obesity was demonstrated by selective knockout of the leptin receptor (LepR) in VAN; mice express an obesogenic phenotype. Obesity and its resultant health consequences are a major worldwide health problem. Effective or preventative treatments for obesity are limited. Our findings have filled the gap in our knowledge of the mechanism of GLP-1 and leptin signaling on VAN. Understanding the physiology regulating feeding behavior is imperative in developing non-invasive anti-obesity treatments
Araújo, Michella Soares Coelho. "Obesidade e resistência à insulina induzida pela restrição crônica no consumo de sal em ratos Wistar: efeitos sobre o balanço energético, sistema renina-angiotensina (SRA) e sinalização da insulina." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/42/42136/tde-15012007-134042/.
Повний текст джерелаRestriction of sodium chloride intake has been associated with insulin resistance (INS-R) and obesity. The molecular mechanisms by which the low salt diet (LSD) can induce INS-R and obesity have not yet been established.The aim of the present study was to evaluate the influences of salt intake on body weight (BW) and on insulin signaling in liver, muscle and white adipose tissue (WAT). Wistar rats were fed a LSD, normal (NSD), or high (HSD) salt diet since weaning. At 12 weeks of age, BW, blood pressure(BP),energy balance, food intake, plasma glucose and angiotesin II (ANGIO II), and hormonal profile were evaluated. Afterward, motor activity, HOMA index, uncoupling protein 1 expression (UCP-1) and tissue adipose ANGIO II content was determined. The early steps of insulin signaling (IR: insulin receptor, IRS-1 and IRS-2: IR substrate 1 and 2, PI-3K: phosphatidylinositol 3-kinase), Akt (protein kinase B) phosphorylation, JNK (c-jun NH2-terminal kinase) activation and IRS-1ser307 (serine 307 of IRS-1) phosphorylation were evaluated by immunoprecipitation and immunoblotting. LSD increased BW, visceral adiposity, blood glucose, insulin, leptin, plasma ANGIO II and its content in BAT. Otherwise, LSD decreased food intake, energy expenditure, UCP-1 expression, adiponectin and ANGIO II content in WAT. Motor activity was not influenced by the dietary salt content. In LSD, a decreasing in IR/PI-3K/Akt/Foxo1 was observed in liver and muscle and an increase in this pathway was showed in adipose tissue. JNK activity and IRS-1ser307 phosphorylation were higher in liver and muscle. In conclusion, LSD induced obesity and insulin resistance due to changes in energy expenditure, SRA and insulin signaling. The INS-R is tissuespecific and is accompanied by JNK activation and IRS-1ser307 phosphorylation.
Papazoglou, Ioannis. "Cross-talk between insulin and serotonin signaling in the brain : Involvement of the PI3K/Akt pathway and behavioral consequences in models of insulin resistance." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T039/document.
Повний текст джерелаInsulin and serotonin (5-HT) are two key players in the maintenance of energy homeostasis which is controlled by the hypothalamus. In this brain region, insulin mediates numerous metabolic effects via the activation of the PI3K/Akt signaling pathway. 5-HT exerts similar biological properties by acting in the hypothalamus but the signaling pathways accountable for these effects are still unclear. Moreover, it has been reported that 5-HT induces the activation of the PI3K/Akt pathway in the hippocampus and the inhibition of GSK3β, suggesting this action as a potential mechanism for the antidepressant effects of this neurotransmitter.The main objectives of this thesis were to study 1/ the serotonin-induced activation of the PI3K/Akt in the hypothalamus of wild type and diabetic rats (Goto-Kakizaki model) and search a potential cross-talk with insulin and, 2/ the mechanisms underlying the high-fat diet induced depression by investigating the role of the phosphorylation of Akt and GSK3β by 5-HT, insulin and leptin in the hippocampus of rats.Here, we show that 5-HT triggers the PI3K/Akt signaling pathway in the rat hypothalamus, and that this activation is attenuated in insulin-resistant conditions, suggesting a cross-talk between insulin and 5-HT. Moreover, we reported that high-fat diet feeding induces a reversible depressive-like behavior, which may involve the PI3K/Akt/GSK3β pathway in subgranular neurons of the dentate gyrus. In conclusion, the activation of the PI3K/Akt pathway and its target GSK3β by 5-HT in the hypothalamus and in the dentate gyrus, respectively, can be impaired in insulin-/leptin-resistant states, which may underlie a link between metabolic diseases and depression
Ardid, Ruiz Andrea. "Phenolic compounds as modulators of leptin signalling pathway in peripheral tissues." Doctoral thesis, Universitat Rovira i Virgili, 2018. http://hdl.handle.net/10803/664719.
Повний текст джерелаLa obesidad es una patología extendida por todo el mundo y uno de los principales factores relacionados con otras enfermedades crónicas. Las terapias convencionales utilizadas para prevenir o paliar la obesidad, ejercicio y reducción del consumo de alimentos muy energéticos, son inefectivas. En este sentido, el uso de compuestos bioactivos como son los polifenoles, metabolitos secundarios de las plantas con un amplio espectro de beneficios para la salud, se presenta como una estrategia innovadora para combatir la obesidad. La leptina es una hormona secretada proporcionalmente a la cantidad de adipocitos y que actúa principalmente en el sistema nervioso central controlando el balance energético. En este proceso, el transporte de la leptina a través de la barrera hematoencefálica es importante. También está implicada en la regulación de la homeóstasis periférica, modulando el metabolismo lipídico y de los carbohidratos. La obesidad está relacionada con un deterioro de la acción de la leptina, la resistencia a la leptina, causando hiperleptinemia y un incremento en la ingesta energética. En este contexto, el objetivo de la tesis es identificar compuestos fenólicos con la capacidad de restaurar la condición de obesidad-resistencia a la leptina causada en tejidos periféricos (hígado, músculo esquelético y tejido adiposo epididimal) y que puedan incrementar el transporte de la leptina a través de la barrera hematoencefálica. Nuestros resultados demuestran los efectos del resveratrol y sus metabolitos actuando en la vía periférica de señalización de la leptina, disminuyendo la grasa corporal en un modelo de rata obesa. Además, el resveratrol restaura la sensibilidad a la leptina en un modelo esteatótico de células cancerígenas hepáticas humanas, incrementando el contenido del receptor de la leptina. Finalmente, se ha descrito la capacidad de diferentes compuestos fenólicos para incrementar el contenido del receptor de la leptina y la capacidad de éstos en proteger contra el daño inducido por citoquinas pro-inflamatorias en células endoteliales de cerebro de rata. Esta investigación proporciona una información innovadora que puede ser útil para la industria de alimentos funcionales, identificando compuestos bioactivos que pueden ser usados para tratar potencialmente la obesidad y sus patologías asociadas.
Obesity is a current and worldwide extended problem and one of the main factors related with other chronic pathologies. Conventional therapies, normally based on increasing the exercise and reducing the consumption of energy-dense food used to prevent or palliate obesity, are ineffective. In this sense, the use of bioactive compounds as polyphenols, a group of plant secondary metabolites with a wide range of beneficial healthy effects, arises as a novel strategy to combat obesity and its related pathologies. Leptin is a key hormone secreted proportionally by the amount of adipocytes that acts primarily in the central nervous system controlling the energy balance. In this process, leptin transport across the blood-brain barrier is especially important. In addition, leptin is implicated in the regulation of peripheral homeostasis, mainly modulating the lipid and carbohydrate metabolism, in organs such as liver, muscle and white adipose tissue. However, obesity is related with an impaired action of leptin, namely leptin resistance, causing hyperleptinemia and an increase in the energy intake. In this context, the aim of this thesis is to identify phenolic compounds with the capacity to restore the obesogenic-leptin resistance condition caused in peripheral tissues (liver, skeletal muscle and epididymal white adipose tissue) and to increase the leptin transport across the blood-brain barrier. Our results demonstrate the effects of resveratrol and its metabolites acting in the peripheral leptin signalling pathway on reducing body fat accumulation in an obesogenic rat model. Moreover, resveratrol restores the leptin sensitivity in a palmitate-induced model of steatotic human hepatocellular carcinoma cell line by increasing the leptin receptor content. Finally, the capacity of different phenolic compounds to increase the leptin receptor content and to protect against pro-inflammatory cytokine-induced damage in rat brain endothelial cells is described. This research provides novel information that can be useful for the functional food industry identifying bioactive compounds that can be used to potentially treat obesity and its related pathologies.
Ahmed, Meftun. "Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells : Modulation by amino acids, glucagon, caffeine and ryanodine". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1408.
Повний текст джерелаAhmed, Meftun. "Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells : Modulation by amino acids, glucagon, caffeine and ryanodine". Doctoral thesis, Uppsala University, Department of Medical Cell Biology, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1408.
Повний текст джерелаOscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.
Huynh, Frank Khan. "Regulation of glucose and lipid metabolism by hepatic leptin signalling." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42816.
Повний текст джерелаGaronna, Elena. "Leptin-mediated endothelial cell activation : signalling mechanisms and functional relevance." Thesis, Royal Veterinary College (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498254.
Повний текст джерелаMcSloy, Alexandra. "Regulation of macro- and micro-vascular endothelial cell survival by leptin and thrombin: signalling mechanisms and functional relevance." Thesis, Royal Veterinary College (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618292.
Повний текст джерелаHanif, Shahid. "Quantitative expression of genes involved in the leptin receptor-mediated STAT signalling pathway in rodent models of obesity." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272872.
Повний текст джерелаWoolson, Hayley D. "Investigation of the cAMP-mediated inhibitory mechanism on the signalling pathways of 2 cytokines : IL-6 and leptin in endothelial cells." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/648/.
Повний текст джерелаFaßhauer, Martin. "The role of leptin and insulin signaling in the hypothalamic control of liver metabolism." Doctoral thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0001-BBE6-E.
Повний текст джерелаde, Andrade Fernandes Maria Fernanda. "Leptin modulation of locomotor and emotional behaviors : the role of STAT3 signaling in dopamine neurons." Thèse, 2014. http://hdl.handle.net/1866/13547.
Повний текст джерелаThe adipocyte-derived hormone leptin circulates in proportion to the body fat content and transduces its signal through the long form of its receptor via a number of neural pathways, including MAPK, PI3-K, AMPK and JAK2-STAT3. Of note, STAT3 constitutes a key pathway downstream to the leptin receptor by which leptin modulates the expression of genes involved in energy balance. Most research has focused on leptin receptor function within the hypothalamus, in particular leptin receptor function within the arcuate nucleus. However, leptin receptors are also expressed on dopaminergic neurons of the ventral tegmental area, and leptin has been shown to target this brain region to influence feeding, motivation, locomotion, anxiety and dopamine tone. Moreover, leptin activates STAT3 in both dopaminergic and GABAergic neuronal populations. Although these findings contribute to our understanding of the multiple actions of leptin in the central nervous system, it remains to be resolved which cells and leptin receptor signaling pathway mediates the neurobehavioral effects of leptin in the midbrain. Aiming at determining the contribution of STAT3 signaling in midbrain DA neurons, we generated a line of conditional knockout mice in which the main activation site of STAT3 gene (tyr 705) is absent specifically in dopaminergic neurons (STAT3DAT-KO mice). Using this genetic mouse model, we assessed the impact of ablation of STAT3 signaling in dopaminergic neurons on a number of dopamine-related functions, including feeding, locomotion, reward-related behaviors, emotion and nucleus accumbens dopamine release. Interestingly, we observed a sexual dimorphism in the phenotype of STAT3DAT-KO mice. STAT3 signaling in DA neurons mediates the actions of leptin in the midbrain to decrease locomotion and running reward, and to increase dopamine release and availability in male mice. However, it does not modulate emotional behavior. On the other hand, STAT3DAT-KO female mice exhibited increased anxiety-like behavior accompanied by increased plasma corticosterone levels, without changes in behavioral despair relative to littermate controls. However, loss of STAT3 activation in dopaminergic neurons does not modulate locomotor behavior in female mice. Notably, the actions of leptin in the midbrain to influence feeding behavior are not mediated by STAT3 signaling in dopaminergic neurons, as both male and female STAT3DAT-KO mice have normal feeding behavior as compared to littermate controls. Our results demonstrate that STAT3 signaling in dopaminergic neurons mediates the anxiolytic actions of leptin, and support the hypothesis that leptin communicates body energy status (defined as a relationship between energy intake and energy expenditure) to mesolimbic regions to adjust the motivational and rewarding effects of multiple behaviors that serve to either restore or deplete energy stores. In addition, this work highlight the importance of studying cell-type specific modulation of leptin signaling molecules to tease apart pathways and the mechanisms involved in the different neurobehavioral functions of this adipocyte-derived hormone.
Hao-Ting, Hsu. "Leptin interferes ACTH-cAMP signaling on steroid biosynthesis in human NCI-H295 adrenocortical tumor cell line." 2005. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2207200516304800.
Повний текст джерелаHsu, Hao-Ting, and 許皓婷. "Leptin interferes ACTH-cAMP signaling on steroid biosynthesis in human NCI-H295 adrenocortical tumor cell line." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/24298824034705966742.
Повний текст джерела國立臺灣大學
獸醫學研究所
93
Leptin, mainly secreted from adipose tissues surrounding adrenal glands, is proposed to locally control the biosynthesis of adrenal steroid hormones. The human adrenocortical NCI-H295 cells were treated with or without leptin, adrenocorticotropic reagent, or both. Two major adrenal steroid products, progesterone and cortisol secreted in their cultured media were measured by ELISA. Cholera toxin, an activator of cAMP-protein kinase A pathway, mimicked ACTH effect to stimulate the secretion of progesterone and cortisol in time- and dose-dependent fashions. Leptin did not affect basal secretion of both steroid hormones; however, it effectively inhibited ACTH- or cholera toxin-induced secretion of progesterone and cortisol. Furthermore, the induction of cholera toxin on the protein amounts of P450scc, the first and rate-limiting steroidogenic enzyme, 3b-HSD, the essential enzyme for synthesis of bioactive steroids, and P450c21, the critical enzyme in secreting corticoids, were reduced by leptin. Similar inhibition of leptin was observed at the mRNA levels of P450scc and 3b-HSD. The involvement of leptin in regulating CYP11A1 promoter activity was evaluated by 5’-serial deletion. The deletion clones containing CYP11A1 promoter over 1.7 kb were responsive, whereas the shorter clone with 1.5-kb CYP11A1 promoter was silent to cAMP stimulation. The cAMP-inducible promoter activity was decreased by leptin. The inhibition of leptin on cAMP-regulated steroidogenesis and CYP11A1 promoter activity was prevented by the JAK1/2 specific inhibitor AG490 and PI3 kinase specific inhibitor Wortmannin as well as a general PDE inhibitor IBMX and a PDE3 selective inhibitor SKF94836; moreover, leptin failed to interfere the induction of N6-MB-cAMP, a PDE3B resistant cAMP analogue. Collectively, this study demonstrated leptin reduced adrenocorticotropic reagent-induced steroidogenesis possibly through a hypothesized JAK1/2-PI3 kinase-PDE3B-cAMP pathway.
Kao, Pei-Chen, and 高培甄. "The effects of high sucrose and high fat diet on cortical inflammation and hypothalamic leptin signaling of APP/PS1 transgenic mice." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/41842275740799583060.
Повний текст джерела國立陽明大學
神經科學研究所
104
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease with unknown etiology. The hallmarks of AD include β-amyloid (Aβ) containing senile plaques and neurofibrillary tangles in the brain. Neuroinflammation, neuronal insulin resistance and impaired energy homeostasis have been reported to modulate AD pathogenesis. The food intake and energy expenditure majorly modulated by the hypothalamus are impaired in AD patients, but underlying mechanisms remain unclear. Western diet contains high sucrose and high fat. High fat diet (HFD) induces obesity and accelerates the AD pathogenesis, but less is known about the impact of high sucrose diet (HSD) and HFD on central leptin signaling and AD pathology. This study is aimed to investigate individual impacts of HSD and HFD on the pathology and leptin signaling of APP/PS1 transgenic mice (AD mice). Wild type (WT) and AD mice fed on HSD, HFD or normal chow diet (NCD) were applied in this study. Compared with NCD, my data showed that HSD and HFD both increased the level of serum Aβ and induced neuroinflammation. HSD elevated the level of cortical Aβ and HFD induced hyperleptinemia and increased soluble leptin receptor. However, no hyperleptinemia and obesity was observed in HSD WT and AD mice, in spite of severe leptin resistance of HSD AD mice was observed in our laboratory. My data suggested that HSD increased soluble leptin receptor but not leptin of both HSD WT and AD mice. Furthermore, the level of soluble leptin receptor of HSD WT was significantly higher than that of HSD AD mice along aging. Nevertheless, both leptin and soluble leptin receptor of HSD WT and AD mice responded comparably in the fasting-refeeding experiment. In conclusion, metabolic stresses induced by HFD and HSD accelerate AD central pathology and modulate on leptin signaling which can be important risk factors of metabolic syndrome and AD.
Poritsanos, Nicole Joanna. "Nutritional regulation of central fat mass and obesity-associated (FTO) expression, and its association with the central melanocortin signaling in the regulation of energy homeostasis." 2010. http://hdl.handle.net/1993/4294.
Повний текст джерелаKentish, Stephen James. "Obesity induced dysfunction of gastric vagal afferent signalling." Thesis, 2013. http://hdl.handle.net/2440/82617.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Medicine, 2013
Moníková, Veronika. "Cirkadiánní regulace proteinu STAT3 v SCN a vliv leptinu na jeho aktivaci v SCN, v jiných částech hypotalamu a epifýze." Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-343801.
Повний текст джерела