Journal articles on the topic 'Adipogensi'
To see the other types of publications on this topic, follow the link: Adipogensi.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Adipogensi.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Dong, Hua, Wenfei Sun, Yang Shen, Miroslav Baláz, Lucia Balázová, Lianggong Ding, Mona Löffler, et al. "Identification of a regulatory pathway inhibiting adipogenesis via RSPO2." Nature Metabolism 4, no. 1 (January 2022): 90–105. http://dx.doi.org/10.1038/s42255-021-00509-1.
Full textAbstract:
AbstractHealthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142+ cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis.
2
Moseti, Dorothy, Alemu Regassa, Chongxiao Chen, Karmin O, and Woo Kyun Kim. "25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells." International Journal of Molecular Sciences 21, no. 2 (January 9, 2020): 412. http://dx.doi.org/10.3390/ijms21020412.
Full textAbstract:
Understanding of adipogenesis is important to find remedies for obesity and related disorders. In addition, it is also critical in bone disorders because there is a reciprocal relationship between adipogenesis and osteogenesis in bone micro-environment. Oxysterols are pro-osteogenic and anti-adipogenic molecules via hedgehog activation in pluripotent bone marrow stomal cells. However, no study has evaluated the role of specific oxysterols in C3H10T1/2 cells, which are a good cell model for studying osteogenesis and adipogenesis in bone-marrows. Thus, we investigated the effects of specific oxysterols on adipogenesis and expression of adipogenic transcripts in C3H10T1/2 cells. Treatment of cells with DMITro significantly induced mRNA expression of Pparγ. This induction was significantly inhibited by 25-HC. The expression of C/cepα, Fabp4 and Lpl was also inhibited by 25-HC. To determine the mechanism by which 25-HC inhibits adipogenesis, the effects of the hedgehog signalling pathway inhibitor, cyclopamine and CUR61414, were evaluated. Treatment of C3H10T1/2 cells with DMITro + cyclopamine or DMITro + CUR61414 for 96h did not modulate adipocyte differentiation; cyclopamine and CUR61414 did not reverse the inhibitory effects of 25-HC, suggesting that the canonical hedgehog signalling may not play a role in the anti-adipogenic effects of 25-HC in C3H10T1/2 cells. In addition, LXR agonist did not inhibit adipogenesis, but 25-HC strongly inhibits adipogenesis of C3H10T1/2 cells. Our observations showed that 25-HC was the most potent oxysterol in inhibiting adipogenesis and the expression of key adipogenic transcripts in C3H10T1/2 cells among the tested oxysterols, suggesting its potential application in providing an intervention in osteoporosis and obesity. We also report that the inhibitory effects of 25-HC on adipogenic differentiation in C3H10T1/2 cells are not mediated by hedgehog signaling and LXR.
3
Baskan, Oznur, Gulistan Mese, and Engin Ozcivici. "Low-intensity vibrations normalize adipogenesis-induced morphological and molecular changes of adult mesenchymal stem cells." Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 231, no. 2 (January 10, 2017): 160–68. http://dx.doi.org/10.1177/0954411916687338.
Full textAbstract:
Bone marrow mesenchymal stem cells that are committed to adipogenesis were exposed daily to high-frequency low-intensity mechanical vibrations to understand molecular, morphological and ultrastructural adaptations to mechanical signals during adipogenesis. D1-ORL-UVA mouse bone marrow mesenchymal stem cells were cultured with either growth or adipogenic medium for 1 week. Low-intensity vibration signals (15 min/day, 90 Hz, 0.1 g) were applied to one group of adipogenic cells, while the other adipogenic group served as a sham control. Cellular viability, lipid accumulation, ultrastructure and morphology were determined with MTT, Oil-Red-O staining, phalloidin staining and atomic force microscopy. Semiquantitative reverse transcription polymerase chain reaction showed expression profile of the genes responsible for adipogenesis and ultrastructure of cells. Low-intensity vibration signals increased viability of the cells in adipogenic culture that was reduced significantly compared to quiescent controls. Low-intensity vibration signals also normalized the effects of adipogenic condition on cell morphology, including area, perimeter, circularization and actin cytoskeleton. Furthermore, low-intensity vibration signals reduced the expression of some adipogenic markers significantly. Mesenchymal stem cells are sensitive and responsive to mechanical loads, but debilitating conditions such as aging or obesity may steer mesenchymal stem cells toward adipogenesis. Here, daily application of low-intensity vibration signals partially neutralized the effects of adipogenic induction on mesenchymal stem cells, suggesting that these signals may provide an alternative and/or complementary option to reduce fat deposition.
4
Yu, Hyung-Seok, Won-Ju Kim, Won-Young Bae, Na-Kyoung Lee, and Hyun-Dong Paik. "Inula britannica Inhibits Adipogenesis of 3T3-L1 Preadipocytes via Modulation of Mitotic Clonal Expansion Involving ERK 1/2 and Akt Signaling Pathways." Nutrients 12, no. 10 (October 3, 2020): 3037. http://dx.doi.org/10.3390/nu12103037.
Full textAbstract:
The flower of Inula britannica contains various phenolic compounds with prophylactic properties. This study aimed to determine the anti-adipogenic effect of an I. britannica flower aqueous extract (IAE) and its underlying mechanisms in the 3T3-L1 preadipocytes and to identify the phenolic compounds in the extract. Treatment with IAE inhibited the adipogenesis of 3T3-L1 preadipocytes by showing a dose-dependently suppressed intracellular lipid accumulation and significantly mitigated expression levels of lipogenesis- and adipogenesis-associated biomarkers including transcription factors. IAE exerted an anti-adipogenic effect through the modulation of the early phases of adipogenesis including mitotic clonal expansion (MCE). Treatment with IAE inhibited MCE by arresting the cell cycle at the G0/G1 phase and suppressing the activation of MCE-related transcription factors. Furthermore, IAE inhibited adipogenesis by regulating the extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Protocatechuic acid, chlorogenic acid, kaempferol-3-O-glucoside, and 6-methoxyluteolin, which are reported to exhibit anti-adipogenic properties, were detected in IAE. Therefore, modulation of early phases of adipogenesis, especially MCE, is a key mechanism underlying the anti-adipogenic activity of IAE. In summary, the anti-obesity effects of IAE can be attributed to its phenolic compounds, and hence, IAE can be used for the development of anti-obesity products.
5
Kwon, Young-Nam, Won Kon Kim, Sang-Hak Lee, Keewon Kim, Eun Young Kim, Tai Hwan Ha, HyoukSoo Han, and Kwang-Hee Bae. "Monitoring of adipogenic differentiation at the single-cell level using atomic force microscopic analysis." Spectroscopy 26, no. 6 (2011): 329–35. http://dx.doi.org/10.1155/2011/707216.
Full textAbstract:
Adipogenesis plays an important role in energy homeostasis by storing excess energy as lipid droplets. However, these reservoirs are implicated in a host of major human health problems, such as obesity. Elucidation of the mechanisms underlying adipogenesis is thus crucial to overcome these problems. The preadipocyte cell lines represent an optimal model to examine adipogenesis. Cells differentiate into adipocytes with various speeds of conversion and fat accumulation. Here, we have presented a novel method for detecting adipogenic differentiation at the single-cell level using atomic force microscopic analysis. Data obtained with this method revealed a good correlation between membrane stiffness and the degree of adipogenic differentiation. Although we could not determine the underlying cause for membrane stiffness reduction during adipogenic differentiation, the technique clearly offers advantages over the existing detection systems, such as lipid drop staining and extraction. Furthermore, the degree of adipogenic differentiation at the single-cell level can be detected with this method.
6
Zhang, Ziang, Rongmei Qu, Tingyu Fan, Jun Ouyang, Feng Lu, and Jingxing Dai. "Stepwise Adipogenesis of Decellularized Cellular Extracellular Matrix Regulates Adipose Tissue-Derived Stem Cell Migration and Differentiation." Stem Cells International 2019 (November 6, 2019): 1–11. http://dx.doi.org/10.1155/2019/1845926.
Full textAbstract:
Microenvironmental factors can modulate the cellular status of adipose tissue-derived stem cells (ASCs). In response to microenvironmental changes, cells can remodel extracellular matrix (ECM) proteins, which play an important role in regulating cell behaviors. During adipogenic differentiation, ECM components secreted from ASCs remodel dramatically. To evaluate the role of stepwise adipogenesis-induced cellular secretion of ECM on the behavior of ASCs, we cultured ASCs in growth and adipogenic media, and ECM secreted from cells was characterized and decellularized. The ASCs were then reseeded on decellularized ECM (d-ECM) to determine the regulatory effects of ECM on cellular behaviors. During adipogenesis, cell-secreted ECM underwent remodeling characterized by conversion from fibronectin-rich ECM to laminin-rich ECM. The cellular status of ASCs was tested after reseeding on decellularized ECM. When reseeded on growth d-ECM, ASCs exhibited greater migration ability. In contrast, ASCs seeded on adipogenic d-ECM underwent adipogenic differentiation. In addition, integrin subunit αv and integrins α6 and α7 were detected at significantly greater levels in ASCs cultured on growth and adipogenic d-ECM, respectively, suggesting that integrins play an important role in ASC migration and adipogenesis. This study demonstrated that stepwise adipogenesis-induced ECM production plays an important role in ASC migration and differentiation. In addition, this study provided a strategy to achieve precise regulation of stem cell function in adipose tissue engineering.
7
Kirchner, Séverine, Tiffany Kieu, Connie Chow, Stephanie Casey, and Bruce Blumberg. "Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes." Molecular Endocrinology 24, no. 3 (March 1, 2010): 526–39. http://dx.doi.org/10.1210/me.2009-0261.
Full textAbstract:
Abstract The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor γ (PPARγ). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARγ activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARγ antagonists, suggesting that activation of PPARγ mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero showed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARγ target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time.
8
Liu, Zhenhua, Peng Wang, Shuizhong Cen, Liangbin Gao, Zhongyu Xie, Xiaohua Wu, Hongjun Su, Yanfeng Wu, and Huiyong Shen. "Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis." Stem Cells International 2019 (November 18, 2019): 1–13. http://dx.doi.org/10.1155/2019/4143167.
Full textAbstract:
Objective. To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. Methods. MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-γ, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. Protein levels of adipogenic markers and signaling pathway-related molecules were assessed via Western blotting. Levels of bone morphogenetic proteins 4, 6, 7, and 9 were determined using enzyme-linked immunosorbent assays. Lentiviruses encoding short hairpin RNAs (shRNAs) were constructed to reverse abnormal bone morphogenetic protein receptor 1A (BMPR1A) expression and evaluate its role in abnormal ASMSC adipogenic differentiation. Bone marrow fat content was assessed using hematoxylin and eosin (HE) staining. BMPR1A expression in bone marrow MSCs was measured using immunofluorescence staining. Results. ASMSCs exhibited a greater adipogenic differentiation capacity than HDMSCs. During adipogenesis, ASMSCs expressed BMPR1A at higher levels, which activated the BMP-pSmad1/5/8 signaling pathway and increased adipogenesis. BMPR1A silencing using an shRNA eliminated the difference in adipogenic differentiation between HDMSCs and ASMSCs. Moreover, HE and immunofluorescence staining showed higher bone marrow fat content and BMPR1A expression in patients with AS than in healthy donors. Conclusion. Increased BMPR1A expression induces abnormal ASMSC adipogenic differentiation, potentially contributing to fat metaplasia and thus new bone formation in patients with AS.
9
Russell, T., C. Bridgewood, A. Khan, A. S. Rao, P. Loughenbury, P. Millner, R. Dunsmuir, A. Altaie, E. Jones, and D. Mcgonagle. "SAT0350 A ROLE FOR IL-17A IN THE SUPPRESSION OF SPINAL ENTHESEAL MESENCHYMAL STEM CELL ADIPOGENESIS WHILST SIMULTANEOUSLY FACILITATING OSTEOGENESIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1121.1–1121. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2820.
Full textAbstract:
Background:Fat formation in the bone adjacent to the enthesis is an important but poorly characterised intermediate stage in new bone formation that occurs in the spine in AS. We and others have previously reported that IL-17A can increase mesenchymal stem cell (MSC) mediated osteogenesis in normal and AS spinal tissue (1, 2).Objectives:Herein we investigate the impact of IL-17A & TNF on MSC adipogenesis from spinal enthesis tissue.Methods:Samples from healthy spinous process and interspinous ligament (n=14, median age = 53) were separated into the peri-entheseal bone (PEB) and entheseal soft tissue (EST) & enzymatically digested. Minimally passaged (<p3) MSCs were cultured in a complete adipogenic media, with some cultures supplemented with either IL-17A (50ng/ml), TNF (1ng/ml) or IL-17A & TNF for 3 weeks. Adipogeneis was quantitatively assessed by Oil Red O staining at day 21. IL-17A’s effect on adipogeneis was further investigated by RNA extractions at Day 0, 3, 5, 7, 15 & 21 with supporting Oil Red O staining. 48 adipogenic and IL-17A target genes were used to investigate adipogenic progression and IL-17A effects on it over 21 day adipogenic differentiation.Results:EST MSCs have a significantly higher adipogenic potential than matched PEB MSCs (n=14, p<0.001). TNF and IL-17A both cause significant decreases (all p<0.01, n=5) in adipogenesis for both PEB and EST MSCs. EST MSCs produced lipid vesicles by day-3 post-induction, with significant inhibition by IL-17A (p<0.01, n=4) seen from day 15 onwards. IL-17A caused a significant decrease in overall Oil Red O staining, and it changed the morphology of lipid vesicles with a majority of cells consistent with immature pre-adipocytes. This was supported by gene expression data, which indicated significant decreases in transcripts encoding vesicle fusion proteins (CIDEC p<0.05, PLIN1 p<0.01). PLIN1 also aids protection against lipolysis (4). Transcripts associated with osteogenesis (CEBPβ (3)) and MSC stromal support (CXCL12) were significantly upregulated in adipogenically-induced cultures stimulated with IL-17A when compared to control adipogenic media. TNF & IL-17A combination demonstrated that IL-17A drove the vesicle morphology changes, with TNF alone not showing the same vesicle changes.Conclusion:Given the inverse link between MSC mediated osteogeneis & adipogenesis, these findings reveal a role of IL-17A especially on EST MSCs. The rapid formation of adipocytes seen in EST MSCs may be relevant to MRI determined peri-entheseal bone “shiny corners” due to post inflammation fat accumulation. Elevated transcripts associated with pre-adipocytes & undifferentiated MSCs support the idea of plasticity between early osteogenesis & adipogenesis. Downregulation of transcripts for proteins associated with protection against lipolysis allows for the rationalising of the gradual loss of the shiny corners seen in AS preceding subsequent new bone formation.References:[1]RUSSELL, T., A. WATAD, C. BRIDGEWOOD, A. KHAN, A.S. RAO, P. LOUGHENBURY, P. MILNER, R. DUNSMUIR, T. BABOOLAL, E. JONES, R. CUTHBERT and D. MCGONAGLE. IL-17A Induces Distinct Functional Differences Between Two Novel Mesenchymal Stem Cell Populations Identified at the Human Enthesis.Arthritis Rheumatol, 2019, 71 Suppl 10, pp.1-5362.[2]JO, S., S.E. WANG, Y.L. LEE, S. KANG, B. LEE, J. HAN, I.H. SUNG, Y.S. PARK, S.C. BAE and T.H. KIM. IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis.Arthritis Res Ther, 2018, 20(1), p.115.[3]AHMED, M. and S.L. GAFFEN. IL-17 in obesity and adipogenesis.Cytokine Growth Factor Rev, 2010, 21(6), pp.449-53.[4]HANSEN, J.S., S. DE MARE, H.A. JONES, O. GORANSSON and K. LINDKVIST-PETERSSON. Visualization of lipid directed dynamics of perilipin 1 in human primary adipocytes.Sci Rep, 2017, 7(1), p.15011.Disclosure of Interests:Tobias Russell Grant/research support from: Novartis UK Investigator Initiated non-clinical research funding support, Charlie Bridgewood: None declared, Almas Khan: None declared, Abhay S Rao: None declared, Peter Loughenbury: None declared, Peter Millner: None declared, Robert Dunsmuir: None declared, Ala Altaie: None declared, Elena Jones: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC
10
da Silva, Carina, Chrisna Durandt, Karlien Kallmeyer, Melvin A. Ambele, and Michael S. Pepper. "The Role of Pref-1 during Adipogenic Differentiation: An Overview of Suggested Mechanisms." International Journal of Molecular Sciences 21, no. 11 (June 9, 2020): 4104. http://dx.doi.org/10.3390/ijms21114104.
Full textAbstract:
Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an early negative regulator of adipogenic differentiation. In this review, we briefly discuss the adipogenic differentiation potential of MSCs derived from two different sources, namely adipose-derived stromal/stem cells (ASCs) and Wharton’s Jelly derived stromal/stem cells (WJSCs). We then discuss the function and suggested mechanisms of action of Pref-1 in regulating adipogenesis, as well as current findings regarding Pref-1’s role in human adipogenesis.
11
Hu, Xiaoming, Yuanfei Zhou, Yang Yang, Jie Peng, Tongxing Song, Tao Xu, Hongkui Wei, Siwen Jiang, and Jian Peng. "Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment." Open Biology 6, no. 6 (June 2016): 160065. http://dx.doi.org/10.1098/rsob.160065.
Full textAbstract:
Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo . RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 ( STAT1 ), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment.
12
Kawai, Masanobu, Noriyuki Namba, Sotaro Mushiake, Yuri Etani, Riko Nishimura, Makoto Makishima, and Keiichi Ozono. "Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARγ pathway." Journal of Molecular Endocrinology 38, no. 1 (January 2007): 19–34. http://dx.doi.org/10.1677/jme.1.02154.
Full textAbstract:
Growth hormone-deficient (GHD) patients show a decreased number of adipocytes, which is normalized by GH replacement, indicating an adipogenic effect of GH. However, the precise mechanisms underlying this effect remain to be clarified. In this study, we investigated the adipogenic effect of GH. GH stimulated MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced adipogenesis of 3T3-L1 cells with early induction of peroxisome proliferator-activated receptors (PPAR)γ2 expression. This adipogenic effect of GH was suppressed by overexpression of Stat5A mutant (Stat5A-Y694F), a transcriptional suppressor for the GH–Stat5A/5B signaling pathway, with the reduction of PPARγ2 expression. Next, we investigated the relationship between Stat5A/5B and CCAAT/enhancer binding protein (C/EBP)β/δ orPPARγ in 3T3-L1 cells. Stat5A/5B stimulated C/EBPβ- and C/EBPδ-induced adipogenesis with enhancement of PPARγ2 expression. In addition, Stat5A/5B enhanced the transcriptional activity of C/EBPβ/δ in the PPARγ gene promoter. Furthermore, Stat5A/5B stimulated PPARγ-induced adipogenesis and enhanced the transcriptional activity of PPARγ. These results suggest that the GH–Stat5A/5B signaling pathway stimulates adipogenesis in cooperation with C/EBPβ/δ and PPARγ. To completely understand the effect of GH, cDNA microarray analysis was performed to screen genes affected by GH during MDI-induced adipogenesis. Among 4277 genes, 18 and 19 genes were up- and down-regulated respectively. cDNA microarray analysis also indicated the up-regulation of PPARγ and the modulation of expression of genes coding for growth factors or growth factor receptors, suggesting that GH stimulates adipogenesis in association with the modulation of cell growth. Thus, the GH–Stat5A/B signaling pathway stimulates adipogenesis through two distinct steps. In addition, cDNA microarray data provide us the further insights underlying the adipogenic effect of GH.
13
Xie, Linjun, Liying Zou, Jie Chen, and Youxue Liu. "All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling." International Journal of Endocrinology 2020 (January 31, 2020): 1–11. http://dx.doi.org/10.1155/2020/6525787.
Full textAbstract:
Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid (atRA, the active form of vitamin A) inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1 (FOS like 1, AP-1 transcription factor subunit) in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing Fra1 (ad-fra1) or silenced for Fra1 (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes (Pparg2, Cebpa) and adipogenesis-associated genes (Cd36, Fabp, Lpl, and Plin); atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in Fra1-silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates Fra1 and FRA1 directly regulates Pparg2 and Cebpa. The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.
14
Liu, Xuenan, Zheng Li, Hao Liu, Yuan Zhu, Dandan Xia, Siyi Wang, Ranli Gu, Ping Zhang, Yunsong Liu, and Yongsheng Zhou. "Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway." Stem Cells International 2020 (March 16, 2020): 1–12. http://dx.doi.org/10.1155/2020/1540905.
Full textAbstract:
Objectives. Flufenamic acid (FFA) is a representative of the fenamic acids, an important group of NSAIDs. In the present study, we study the effects of FFA on adipogenesis of human mesenchymal stem cells (MSCs) and we explore the potential mechanism. Methods. To investigate the effects of FFA on adipogenic differentiation of hMSCs, human adipose-derived stem cells (hASCs) and human bone marrow mesenchymal stem cells (hBMMSCs), representative of hMSCs, were treated with FFA during adipogenic differentiation in vitro. The effects of FFA in vivo were evaluated using a heterotopic adipose formation assay in nude mice as well as ovariectomized (OVX) and aged mice. To explore the mechanism of FFA, Western blot was used to determine activation of the PI3K/AKT signaling pathway. Results. Our results demonstrate that, at certain concentrations, FFA inhibited adipogenesis of human MSCs both in vitro and in vivo. Mechanistically, FFA inhibited adipogenesis of human MSCs by inhibiting the PI3K/AKT pathway. Conclusions. The present study indicated that FFA could be used to inhibit adipogenesis of human MSCs in tissue engineering and diseases related to excessive adipogenic differentiation of MSCs.
15
Kusuyama, Joji, Tomokazu Ohnishi, Kenjiro Bandow, Muhammad Subhan Amir, Kaori Shima, Ichiro Semba, and Tetsuya Matsuguchi. "Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation." Biochemical Journal 474, no. 20 (October 5, 2017): 3421–37. http://dx.doi.org/10.1042/bcj20170332.
Full textAbstract:
Adipogenic differentiation plays a vital role in energy homeostasis and endocrine system. Several transcription factors, including peroxisome proliferator-activated receptor gamma 2 and CCAAT–enhancer-binding protein (C/EBP) α, β, and δ, are important for the process, whereas the stage-specific intracellular signal transduction regulating the onset of adipogenesis remains enigmatic. Here, we explored the functional role of c-jun N-terminal kinases (JNKs) in adipogenic differentiation using in vitro differentiation models of 3T3-L1 cells and primary adipo-progenitor cells. JNK inactivation with either a pharmacological inhibitor or JNK2-specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the down-regulation of Adiponectin, fatty acid protein 4 (Fabp4), Pparg2, and C/ebpa expressions. Conversely, increased adipogenesis was observed by the inducible overexpression of p46JNK2 (JNK2-1), whereas it was not observed by that of p54JNK2 (JNK2-2), indicating a distinct role of p46JNK2. The essential role of JNK appears restricted to the early stage of adipogenic differentiation, as JNK inhibition in the later stages did not influence adipogenesis. Indeed, JNK phosphorylation was significantly induced at the onset of adipogenic differentiation. As for the transcription factors involved in early adipogenesis, JNK inactivation significantly inhibited the induction of C/ebpd, but not C/ebpb, during the initial stage of adipogenic differentiation. JNK activation increased C/ebpd mRNA and protein expression through the induction and phosphorylation of activating transcription factor 2 (ATF2) that binds to a responsive element within the C/ebpd gene promoter region. Taken together, these data indicate that constitutive JNK activity is specifically required for the initial stage differentiation events of adipocytes.
16
Bonilauri, Bernardo, Amanda C. Camillo-Andrade, Marlon D. M. Santos, Juliana de S. da G. Fischer, Paulo C. Carvalho, and Bruno Dallagiovanna. "Proteogenomic Analysis Reveals Proteins Involved in the First Step of Adipogenesis in Human Adipose-Derived Stem Cells." Stem Cells International 2021 (December 16, 2021): 1–14. http://dx.doi.org/10.1155/2021/3168428.
Full textAbstract:
Background. Obesity is characterized as a disease that directly affects the whole-body metabolism and is associated with excess fat mass and several related comorbidities. Dynamics of adipocyte hypertrophy and hyperplasia play an important role in health and disease, especially in obesity. Human adipose-derived stem cells (hASC) represent an important source for understanding the entire adipogenic differentiation process. However, little is known about the triggering step of adipogenesis in hASC. Here, we performed a proteogenomic approach for understanding the protein abundance alterations during the initiation of the adipogenic differentiation process. Methods. hASC were isolated from adipose tissue of three donors and were then characterized and expanded. Cells were cultured for 24 hours in adipogenic differentiation medium followed by protein extraction. We used shotgun proteomics to compare the proteomic profile of 24 h-adipogenic, differentiated, and undifferentiated hASC. We also used our previous next-generation sequencing data (RNA-seq) of the total and polysomal mRNA fractions of hASC to study posttranscriptional regulation during the initial steps of adipogenesis. Results. We identified 3420 proteins out of 48,336 peptides, of which 92 proteins were exclusively identified in undifferentiated hASC and 53 proteins were exclusively found in 24 h-differentiated cells. Using a stringent criterion, we identified 33 differentially abundant proteins when comparing 24 h-differentiated and undifferentiated hASC (14 upregulated and 19 downregulated, respectively). Among the upregulated proteins, we shortlisted several adipogenesis-related proteins. A combined analysis of the proteome and the transcriptome allowed the identification of positive correlation coefficients between proteins and mRNAs. Conclusions. These results demonstrate a specific proteome profile related to adipogenesis at the beginning (24 hours) of the differentiation process in hASC, which advances the understanding of human adipogenesis and obesity. Adipogenic differentiation is finely regulated at the transcriptional, posttranscriptional, and posttranslational levels.
17
Kim, Mi-Kyoung, Hyun-Joo Park, Yeon Kim, Soo-Kyung Bae, Hyung Kim, and Moon-Kyoung Bae. "Involvement of Gastrin-Releasing Peptide Receptor in the Regulation of Adipocyte Differentiation in 3T3-L1 Cells." International Journal of Molecular Sciences 19, no. 12 (December 10, 2018): 3971. http://dx.doi.org/10.3390/ijms19123971.
Full textAbstract:
Gastrin-releasing peptide (GRP), a member of bombesin-like peptides, and its receptor (GRP-R) play an important role in various physiological and pathological conditions. In this work, we investigated the role of GRP-R on adipogenesis in 3T3-L1 adipocytes. The expression of GRP-R was significantly increased during the adipocyte differentiation of 3T3-L1 cells. The inhibition of GRP-R by the antagonist RC-3095 affected adipogenesis in 3T3-L1 cells, which reduced lipid accumulation and regulated the expression of adipogenic genes. Moreover, cyclic AMP response element-binding protein (CREB) directly bound to the GRP-R promoter upon exposure to adipogenic stimuli. The down-regulation of GRP-R by the knockdown of CREB inhibited adipocyte differentiation of 3T3-L1 cells. Together these results suggest that the regulation of GRP-R activity or expression has an influence on adipogenesis through regulating adipogenic related genes.
18
Nartey, Michael N. N., Mitsuo Jisaka, Pinky Karim Syeda, Kohji Nishimura, Hidehisa Shimizu, and Kazushige Yokota. "Arachidonic Acid Added during the Differentiation Phase of 3T3-L1 Cells Exerts Anti-Adipogenic Effect by Reducing the Effects of Pro-Adipogenic Prostaglandins." Life 13, no. 2 (January 29, 2023): 367. http://dx.doi.org/10.3390/life13020367.
Full textAbstract:
A linoleic acid (LA) metabolite arachidonic acid (AA) added to 3T3-L1 cells is reported to suppress adipogenesis. The purpose of the present study aimed to clarify the effects of AA added during the differentiation phase, including adipogenesis, the types of prostaglandins (PG)s produced, and the crosstalk between AA and the PGs produced. Adipogenesis was inhibited by AA added, while LA did not. When AA was added, increased PGE2 and PGF2α production, unchanged Δ12-PGJ2 production, and reduced PGI2 production were observed. Since the decreased PGI2 production was reflected in decreased CCAAT/enhancer-binding protein-β (C/EBPβ) and C/EBPδ expression, we expected that the coexistence of PGI2 with AA would suppress the anti-adipogenic effects of AA. However, the coexistence of PGI2 with AA did not attenuate the anti-adipogenic effects of AA. In addition, the results were similar when Δ12-PGJ2 coexisted with AA. Taken together, these results indicated that the metabolism of ingested LA to AA is necessary to inhibit adipogenesis and that exposure of AA to adipocytes during only the differentiation phase is sufficient. As further mechanisms for suppressing adipogenesis, AA was found not only to increase PGE2 and PGF2α and decrease PGI2 production but also to abrogate the pro-adipogenic effects of PGI2 and Δ12-PGJ2.
19
Fuentes, Paula, María José Acuña, Mariana Cifuentes, and Cecilia V. Rojas. "The anti-adipogenic effect of angiotensin II on human preadipose cells involves ERK1,2 activation and PPARG phosphorylation." Journal of Endocrinology 206, no. 1 (May 7, 2010): 75–83. http://dx.doi.org/10.1677/joe-10-0049.
Full textAbstract:
Despite the importance of adipocyte formation for adipose tissue physiology, current knowledge about the mechanisms that regulate the recruitment of progenitor cells to undergo adipogenic differentiation is limited. A role for locally generated angiotensin II emerged from studies with human and murine cells. Preadipose cells from different human fat depots show reduced response to adipogenic stimuli when exposed to angiotensin II. This investigation sought to gain an insight into the intracellular mechanisms involved in the anti-adipogenic response of human preadipose cells from omental fat to angiotensin II. Its effect was evaluated on cells stimulated to adipogenic differentiation in vitro, by assessment of glycerol-3-phosphate dehydrogenase activity and expression of early markers of adipogenesis. Extracellular signal-regulated kinase1,2 (ERK1,2) pathway activation was inferred from the phosphorylated to total ERK1,2 ratio determined by western blot. Exposure to angiotensin II throughout the 10-day differentiation period resulted in a reduced adipogenic response. A similar anti-adipogenic effect was observed when this hormone was present during the first 48 h of induction to differentiation. Angiotensin II treatment had no consequences on CCAAT/enhancer-binding protein β and peroxisome proliferator-activated receptor γ (PPARG) induction, but increased the phosphorylated form of the key adipogenic regulator PPARG. Upon angiotensin II exposure, a raise of phosphorylated ERK1,2 was determined, which was more prominent 8–20 h after induction of adipogenesis (when controls reached negligible values). Chemical inhibition of ERK1,2 phosphorylation prevented angiotensin II-dependent reduction in adipogenesis. These results support the participation of the mitogen-activated protein kinase/ERK1,2 pathway in the anti-adipogenic effect of angiotensin II on preadipose cells from human omental adipose tissue.
20
Wang, Yaning, Yingying Zhang, Xiaotong Su, Hongbao Wang, Wucai Yang, and Linsen Zan. "Cooperative and Independent Functions of the miR-23a~27a~24-2 Cluster in Bovine Adipocyte Adipogenesis." International Journal of Molecular Sciences 19, no. 12 (December 9, 2018): 3957. http://dx.doi.org/10.3390/ijms19123957.
Full textAbstract:
The miR-23a~27a~24-2 cluster is an important regulator in cell metabolism. However, the cooperative and independent functions of this cluster in bovine adipocyte adipogenesis have not been elucidated. In this study, we found that expression of the miR-23a~27a~24-2 cluster was induced during adipogenesis and this cluster acted as a negative regulator of adipogenesis. miR-27a and miR-24-2 were shown to inhibit adipogenesis by directly targeting glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) and diacylglycerol O-acyltransferase 2 (DGAT2), both of which promoted adipogenesis. Meanwhile, miR-23a and miR-24-2 were shown to target decorin (DCN), glucose-6-phosphate dehydrogenase (G6PD), and lipoprotein lipase (LPL), all of which repressed adipogenesis in this study. Thus, the miR-23a~27a~24-2 cluster exhibits a non-canonical regulatory role in bovine adipocyte adipogenesis. To determine how the miR-23a~27a~24-2 cluster inhibits adipogenesis while targeting anti-adipogenic genes, we identified another target gene, fibroblast growth factor 11 (FGF11), a positive regulator of adipogenesis, that was commonly targeted by the entire miR-23a~27a~24-2 cluster. Our findings suggest that the miR-23a~27a~24-2 cluster fine-tunes the regulation of adipogenesis by targeting two types of genes with pro- or anti-adipogenic effects. This balanced regulatory role of miR-23a~27a~24-2 cluster finally repressed adipogenesis.
21
Jung, Yeon-Seop, Yun-Jeong Jeong, Joung-Hee Kim, Chang-Hwan Jeon, and Syng-Ook Lee. "Elecampane (Inula helenium) Root Extract and Its Major Sesquiterpene Lactone, Alantolactone, Inhibit Adipogenesis of 3T3-L1 Preadipocytes." Molecules 27, no. 15 (July 25, 2022): 4765. http://dx.doi.org/10.3390/molecules27154765.
Full textAbstract:
Recent studies have shown that Nur77 and AMPKα play an important role in regulating adipogenesis and isoalantolactone (ISO) dual-targeting AMPKα and Nur77 inhibits adipogenesis. In this study, we hypothesized that Inula helenium (elecampane) root extract (IHE), which contains two sesquiterpene lactones, alantolactone (ALA) and ISO, as major compounds, might inhibit adipogenesis. Here, we found that ALA and IHE simultaneously target AMPKα and Nur77 and inhibited adipogenic differentiation of 3T3-L1 cells, accompanied by the decreased expression of adipocyte markers. Further mechanistic studies demonstrated that IHE shares similar mechanisms of action with ISO that reduce mitotic clonal expansion during the early phase of adipogenic differentiation and decrease expression of cell cycle regulators. These results suggest that IHE inhibits adipogenesis, in part, through co-regulation of AMPKα and Nur77, and has potential as a therapeutic option for obesity and related metabolic dysfunction.
22
Al-Sayegh, M. A., S. R. Mahmood, S. B. Abul Khair, X. Xie, M. El Gindi, T. Kim, A. Almansoori, and P. Percipalle. "β-actin contributes to open chromatin for activation of the adipogenic pioneer factor CEBPA during transcriptional reprograming." Molecular Biology of the Cell 31, no. 23 (November 1, 2020): 2511–21. http://dx.doi.org/10.1091/mbc.e19-11-0628.
Full textAbstract:
We demonstrate that nuclear actin regulates heterochromatin during adipogenesis by mediating Brg1 deposition at specific adipogenic gene loci to ensure binding of the transcription factor CEBPB. This mechanism contributes to CEBPA gene expression during adipogenic transcriptional reprograming.
23
Qi, Renli, Hong Liu, Qi Wang, Jing Wang, Feiyun Yang, Dingbiao Long, and Jinxiu Huang. "Expressions and Regulatory Effects of P38/ERK/JNK Mapks in the Adipogenic Trans-Differentiation of C2C12 Myoblasts." Cellular Physiology and Biochemistry 44, no. 6 (2017): 2467–75. http://dx.doi.org/10.1159/000486169.
Full textAbstract:
Background/Aims: Myoblasts and muscle satellite cells have the potential to transdifferentiate into adipocytes or adipocyte-like cells. Previous studies suggest that mitogen-activated protein kinase (MAPK) is critical to adipogenic trans-differentiation of muscle cells. ERK1/2, P38 and JNK are three major MAPK family members; their activation and regulatory functions during adipogenic trans-differentiation of myoblasts are investigated. Methods: C2C12 myoblasts were cultured and induced for adipogenic trans-differentiation. Activation patterns of MAPKs were assayed using protein microarray and Western blot. Three specific MAPK blockers, U0126, SB20358 and SP600125, were used to block ERK1/2, P38 and JNK during trans-differentiation. Cellular adipogenesis was measured using staining and morphological observations of cells and expression changes in adipogenic genes. Results: Inhibitors reduced phosphorylation of corresponding MAPK and produced unique cellular effects. Suppressing P38 promoted adipogenic trans-differentiation and intensified adipolytic metabolism in differentiated cells. However, inhibition of ERK1/2 had the opposite effects on adipogenesis and no effect on adipolysis. Blocking JNK weakly blocked trans-differentiation but stimulated adipolysis and induced apoptosis. Conclusion: Three MAPKs participate in the regulation of myoblast adipogenic trans-differentiation by controlling adipogenic and adipolysis metabolism.
24
Wang, Zonggui, Zhong Dai, Zhicong Luo, and Changqing Zuo. "Identification of Pyrvinium, an Anthelmintic Drug, as a Novel Anti-Adipogenic Compound Based on the Gene Expression Microarray and Connectivity Map." Molecules 24, no. 13 (June 28, 2019): 2391. http://dx.doi.org/10.3390/molecules24132391.
Full textAbstract:
Obesity is a serious health problem, while the current anti-obesity drugs are not very effective. The Connectivity Map (C-Map), an in-silico drug screening approach based on gene expression profiles, has recently been indicated as a promising strategy for drug repositioning. In this study, we performed mRNA expression profile analysis using microarray technology and identified 435 differentially expressed genes (DEG) during adipogenesis in both C3H10T1/2 and 3T3-L1 cells. Then, DEG signature was uploaded into C-Map, and using pattern-matching methods we discovered that pyrvinium, a classical anthelminthic, is a novel anti-adipogenic differentiation agent. Pyrvinium suppressed adipogenic differentiation in a dose-dependent manner, as evidenced by Oil Red O staining and the mRNA levels of adipogenic markers. Furthermore, we identified that the inhibitory effect of pyrvinium was resulted primarily from the early stage of adipogenesis. Molecular studies showed that pyrvinium downregulated the expression of key transcription factors C/EBPa and PPARγ. The mRNA levels of notch target genes Hes1 and Hey1 were obviously reduced after pyrvinium treatment. Taken together, this study identified many differentially expressed genes involved in adipogenesis and demonstrated for the first time that pyrvinium is a novel anti-adipogenic compound for obesity therapy. Meanwhile, we provided a new strategy to explore potential anti-obesity drugs.
25
Su, Xin, Shuwei Weng, and Daoquan Peng. "New Insights into Apolipoprotein A5 and the Modulation of Human Adipose-derived Mesenchymal Stem Cells Adipogenesis." Current Molecular Medicine 20, no. 2 (January 14, 2020): 144–56. http://dx.doi.org/10.2174/1566524019666190927155702.
Full textAbstract:
Background: The hallmark of obesity is the excessive accumulation of triglyceride (TG) in adipose tissue. Apolipoprotein A5 (ApoA5) has been shown to influence the prevalence and pathogenesis of obesity. However, the underlying mechanisms remain to be clarified. Methods: Human adipose-derived mesenchymal stem cells (AMSCs) were treated with 600 ng/ml human recombinant ApoA5 protein. The effect of ApoA5 on intracellular TG content and adipogenic related factors expression were determined. Furthermore, the effect of ApoA5 on CIDE-C expression was also observed. Results: During the process of adipogenesis, ApoA5 treatment reduced the intracellular accumulation of lipid droplets and the TG levels; meanwhile, ApoA5 down-regulated the expression levels of adipogenic related factors, including CCAAT enhancer-binding proteins α/β (C/EBPα/β), fatty acid synthetase (FAS), and fatty acid-binding protein 4 (FABP4). Furthermore, the suppression of adipogenesis by ApoA5 was mediated through the inhibition of CIDE-C expression, an important factor which promotes the process of adipogenesis. However, over-expressing intracellular CIDE-C could lead to the loss-of-function of ApoA5 in inhibiting AMSCs adipogenesis. Conclusions: In conclusion, ApoA5 inhibits the adipogenic process of AMSCs through, at least partly, down-regulating CIDE-C expression. The present study provides novel mechanisms whereby ApoA5 prevents obesity via AMSCs in humans.
26
Zhu, Endong, Juanjuan Zhang, Jie Zhou, Hairui Yuan, Wei Zhao, and Baoli Wang. "miR-20a-5p promotes adipogenic differentiation of murine bone marrow stromal cells via targeting Kruppel-like factor 3." Journal of Molecular Endocrinology 60, no. 3 (April 2018): 225–37. http://dx.doi.org/10.1530/jme-17-0183.
Full textAbstract:
miR-20a-5p has recently been identified to induce adipogenesis of established adipogenic cell lines in our previous study. However, its role and molecular mechanisms in the regulation of adipocyte lineage commitment of bone marrow-derived stromal cells (BMSCs) still need to be explored. In this report, we demonstrated the expression of miR-20a-5p was promoted gradually during adipogenic differentiation in BMSCs. We also confirmed that miR-20a-5p has a positive function in the adipogenic differentiation of BMSCs by gain-of-function study with overexpression lentivirus or synthetic mimics of miR-20a-5p, and loss-of-function study with sponge lentivirus or synthetic inhibitor of miR-20a-5p. Dual luciferase reporter assay, GFP repression assay and Western blotting suggested Kruppel-like factor 3 (Klf3) was a direct target of miR-20a-5p. Furthermore, siRNA-mediated silencing ofKlf3recapitulated the potentiation of adipogenesis induced by miR-20a-5p overexpression, whereas enhanced expression ofKlf3attenuated the effect of miR-20a-5p. AsKlf3was reported to play an inhibitory role in adipogenesis at the initial stage of differentiation, the findings we present here indicate that miR-20a-5p promotes adipocyte differentiation from BMSCs by targeting and negatively regulatingKlf3in the early phase during the procedure of adipogenesis.
27
Wang, Jing, Junyi Liao, Fugui Zhang, Dongzhe Song, Minpeng Lu, Jianxiang Liu, Qiang Wei, et al. "NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells." Cellular Physiology and Biochemistry 41, no. 2 (2017): 484–500. http://dx.doi.org/10.1159/000456885.
Full textAbstract:
Background: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. Methods: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis. In vivo activity was assessed in an ectopic bone formation model of athymic mice. Results: We demonstrate that Nell1 expression was up-regulated by BMP9. Exogenous Nell1 potentiated BMP9-induced late stage osteogenic differentiation while inhibiting the early osteogenic marker. Forced Nell1 expression enhanced BMP9-induced osteogenic regulators/markers and inhibited BMP9-upregulated expression of adipogenic regulators/markers in MSCs. In vivo ectopic bone formation assay showed that exogenous Nell1 expression enhanced mineralization and maturity of BMP9-induced bone formation, while inhibiting BMP9-induced adipogenesis. Conversely, silencing Nell1 expression in BMP9-stimulated MSCs led to forming immature chondroid-like matrix. Conclusion: Our findings indicate that Nell1 can be up-regulated by BMP9, which in turn accelerates and augments BMP9-induced osteogenesis. Exogenous Nell1 may be exploited to enhance BMP9-induced bone formation while overcoming BMP9-induced adipogenesis in regenerative medicine.
28
Yu, Chieh, Ian W. Peall, Son H. Pham, Rachel K. Okolicsanyi, Lyn R. Griffiths, and Larisa M. Haupt. "Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance." International Journal of Molecular Sciences 21, no. 11 (May 29, 2020): 3884. http://dx.doi.org/10.3390/ijms21113884.
Full textAbstract:
Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation.
29
Jakab, Jelena, Milorad Zjalić, Štefica Mikšić, Ivan Tušek, Vesna Ćosić, Nikola Volarić, Dario Nakić, Aleksandar Včev, and Blaženka Miškić. "Effect of Metformin and Simvastatin in Inhibiting Proadipogenic Transcription Factors." Current Issues in Molecular Biology 43, no. 3 (November 25, 2021): 2082–97. http://dx.doi.org/10.3390/cimb43030144.
Full textAbstract:
Obesity is a multifactorial chronic disease characterized by the excessive accumulation of fat in adipose tissue driven by hypertrophy and hyperplasia of adipocytes through adipogenesis. Adipogenesis plays a key role in the development of obesity and related metabolic disorders, which makes it potential target for the therapeutic approach to obesity. An increasing number of studies confirm the pleiotropic action of the combined treatment with metformin and statins, suggesting their anti-hypertensive, anti-inflammatory, and anti-adipogenic effect. The aim of this study was to analyze the effect of different doses of metformin (MET) and simvastatin (SIM) on the expression of key transcription factors of adipogenesis. Mouse 3T3-L1 preadipocytes were induced to differentiation in adipogenic medium with sustained MET and SIM treatment to assess the effect on adipogenesis. Nine days after initiating adipogenesis, the cells were prepared for further experiments, including Oil Red O staining, RT-PCR, Western blotting, and immunocytochemistry. Treating the cells with the combination of MET and SIM slightly reduced the intensity of Oil Red O staining compared with the control group, and down-regulated mRNA and protein expression of PPARγ, C/EBPα, and SREBP-1C. In conclusion, the inhibitory effect of MET and SIM on adipocyte differentiation, as indicated by decreased lipid accumulation, appears to be mediated through the down-regulation of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding pro-tein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1C).
30
Chen, Chen, Yongdong Peng, Yinglin Peng, Jian Peng, and Siwen Jiang. "miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling." Journal of Molecular Endocrinology 52, no. 3 (June 2014): 311–20. http://dx.doi.org/10.1530/jme-14-0013.
Full textAbstract:
MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein α (Cebpa), peroxisome proliferator-activated receptor γ (Pparg), adipocyte fatty acid binding protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential transcriptional regulators of preadipocyte differentiation and lipid storage in mature adipocytes. Canonical Wnt/β-catenin signaling is recognized as a negative molecular switch during adipogenesis. In the present work we found that miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-135a-5p impairs the expressions of adipogenic marker genes as well as lipid droplet accumulation and triglyceride content, indicating the importance of miR-135a-5p for adipogenic differentiation and adipogenesis. Further studies show that miR-135a-5p directly targets adenomatous polyposis coli (Apc), contributes to the translocation of β-catenin from cytoplasm to nucleus, and then activates the expressions of cyclin D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/β-catenin signaling. In addition, inhibition of APC with siRNA exhibits the same effects as overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/β-catenin signaling by directly targeting Apc. Taken together, these results offer profound insights into the adipogenesis mechanism and the development of adipose tissue.
31
Subhash, Ajith K., Michael Davies, Andrew Gatto, Jacob M. Bogdanov, Rae Lan, Andrew Jensen, Brian T. Feeley, and Frank A. Petrigliano. "Fibro-adipogenesis in Injured Rotator Cuff Muscle." Current Tissue Microenvironment Reports 3, no. 1 (January 8, 2022): 1–9. http://dx.doi.org/10.1007/s43152-021-00033-0.
Full textAbstract:
Abstract Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.
32
Norman, Jennifer Elise, Andrea Gail Marshall, John C. Rutledge, and Sue C. Bodine. "Skeletal Muscle Stromal Cells Derived From MuRF1 Knockout Mice Are Resistant to Adipogenesis." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A57. http://dx.doi.org/10.1210/jendso/bvab048.115.
Full textAbstract:
Abstract Background: Intramuscular adipose tissue has been found to contribute to muscle dysfunction and is associated with a sedentary lifestyle, aging, and glucocorticoid treatment. Muscle ring finger 1 knockout (MuRF1 KO) mice have been shown to be protected from muscle loss following disuse, aging, and glucocorticoid treatment. In this study we used in vitro techniques to determine if MuRF1 KO muscle stromal cells are resistant to adipogenesis. Methods: Stromal cells were isolated from skeletal muscle tissue of MuRF1 KO and wild type mice. These cells were expanded in culture until 70–90% confluent, then differentiated in either a myogenic media formulation (myogenic cultures) or an adipogenic media formulation (adipogenic cultures). Gene expression was analyzed by qRT-PCR, protein content was measured by bicinchoninic acid assay, and triglyceride content was analyzed by colorimetric assay. We also analyzed isolated stromal cells, which had not been expanded in culture, by flow cytometry to identify myogenic satellite cells (SCs) and fibro-adipogenic progenitors (FAPs). Results: Wild type adipogenic cultures had higher expression of Trim63, the gene encoding MuRF1, when compared to wild type myogenic cultures. Adipogenic cultures had higher expression of adipogenic programing and lipid handling genes than myogenic cultures. These adipogenic cultures also had higher triglyceride content than myogenic cultures. The expression of adipogenic programing genes and lipid handling genes were lower in cultures derived from MuRF1 KO mice compared to wild type derived cultures; however, there was no statistically significant difference in the triglyceride content between the two genotypes. Analysis of stromal cell populations by flow cytometry indicated no difference in the FAP:SC ratio between wild type and MuRF1 KO mice. Conclusions: These results indicate that although there are no differences in the ratio of FAPs to SCs in wild type and MuRF1 KO mice, the MuRF1 KO cultures appear to be resistant to adipogenesis. The mechanism behind this resistance to adipogenesis remains to be elucidated.
33
Chen, Yaqian, Qiwen Li, Yuting Liu, Xuelan Chen, Shuang Jiang, Weimin Lin, Yuning Zhang, et al. "AFF4 regulates cellular adipogenic differentiation via targeting autophagy." PLOS Genetics 18, no. 9 (September 23, 2022): e1010425. http://dx.doi.org/10.1371/journal.pgen.1010425.
Full textAbstract:
Transcriptional elongation is a universal and critical step during gene expression. The super elongation complex (SEC) regulates the rapid transcriptional induction by mobilizing paused RNA polymerase II (Pol II). Dysregulation of SEC is closely associated with human diseases. However, the physiological role of SEC during development and homeostasis remains largely unexplored. Here we studied the function of SEC in adipogenesis by manipulating an essential scaffold protein AF4/FMR2 family member 4 (AFF4), which assembles and stabilizes SEC. Knockdown of AFF4 in human mesenchymal stem cells (hMSCs) and mouse 3T3-L1 preadipocytes inhibits cellular adipogenic differentiation. Overexpression of AFF4 enhances adipogenesis and ectopic adipose tissue formation. We further generate Fabp4-cre driven adipose-specific Aff4 knockout mice and find that AFF4 deficiency impedes adipocyte development and white fat depot formation. Mechanistically, we discover AFF4 regulates autophagy during adipogenesis. AFF4 directly binds to autophagy-related protein ATG5 and ATG16L1, and promotes their transcription. Depleting ATG5 or ATG16L1 abrogates adipogenesis in AFF4-overepressing cells, while overexpression of ATG5 and ATG16L1 rescues the impaired adipogenesis in Aff4-knockout cells. Collectively, our results unveil the functional importance of AFF4 in regulating autophagy and adipogenic differentiation, which broaden our understanding of the transcriptional regulation of adipogenesis.
34
Kang, Jianshu, Yunqin Li, Yue Zou, Zhijian Zhao, Linan Jiao, and Hong Zhang. "miR-96-5p Induces Orbital Fibroblasts Differentiation by Targeting Smad7 and Promotes the Development of Thyroid-Associated Ophthalmopathy." Evidence-Based Complementary and Alternative Medicine 2022 (February 27, 2022): 1–11. http://dx.doi.org/10.1155/2022/8550307.
Full textAbstract:
Background. Recent evidence shows that adipogenic differentiation of orbital fibroblasts (OFs) promotes the development of thyroid-associated ophthalmopathy (TAO), an organ-specific immune disease. Furthermore, miR-96-5p has been linked to adipogenic differentiation of C2C12 myoblasts and is significantly correlated with the severity of TAO. The purpose of this study is to look into the role of miR-96-5p in the adipogenesis of OFs with TAO. Methods. The orbital tissues from TAO patients and non-TAO participants were collected, and primary OFs were isolated and cultured for further analysis. miR-96-5p expression was examined using qRT-PCR. The adipogenic differentiation of OFs was then studied. Results. Orbital fibroblasts isolated from adipose tissues of TAO patients (t-OFs) demonstrated greater adipogenic differentiation ability than OFs isolated from adipose tissues of non-TAO participants. miR-96-5p was found to be overexpressed in the orbital tissues of TAO patients and t-OFs. Further research revealed that miR-96-5p, by targeting Smad7, could exacerbate PPAR-γ/C/EBPα signaling-induced adipogenic differentiation of t-OFs. However, inhibiting miR-96-5p could block t-OFs adipogenic differentiation-mediated adipogenesis via Smad7/PPAR-γ/C/EBPα. Conclusions. miR-96-5p plays a critical regulatory role in the development of TAO by targeting Smad7 and promoting adipogenic differentiation of OFs.
35
Baek, Su Cheol, Ki Hong Nam, Sang Ah Yi, Mun Seok Jo, Kwang Ho Lee, Yong Hoon Lee, Jaecheol Lee, and Ki Hyun Kim. "Anti-adipogenic Effect of β-Carboline Alkaloids from Garlic (Allium sativum)." Foods 8, no. 12 (December 12, 2019): 673. http://dx.doi.org/10.3390/foods8120673.
Full textAbstract:
Garlic (Allium sativum L.) is utilized worldwide for culinary and medicinal use and has diverse health benefits. As part of our ongoing research to identify bioactive components from natural resources, phytochemical analysis of the methanolic extract of garlic led to the isolation and characterization of six compounds: Three eugenol diglycosides (1–3) and three β-carboline alkaloids (4–6). In particular, the absolute configurations of β-carboline alkaloids (5 and 6) were established by gauge-including atomic orbital nuclear magnetic resonance chemical shift calculations, followed by DP4+ analysis. Here, we evaluated the effects of compounds 1–6 on 3T3-L1 preadipocyte adipogenesis and lipid metabolism. 3T3-L1 adipocyte differentiation was evaluated using Oil Red O staining; the expression of adipogenic genes was detected using RT-qPCR. Among compounds 1–6, (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (6) inhibited 3T3-L1 preadipocyte adipogenesis and reduced the expression of adipogenic genes (Fabp4, PPARγ, C/EBPβ, Adipsin, and Adipoq). Moreover, it markedly decreased the actylation of α-tubulin, which is crucial for cytoskeletal remodeling during adipogenesis. Anti-adipogenic effects were observed upon treatment with compound 6, not only during the entire process, but also on the first two days of adipogenesis. Additionally, treatment with compound 6 regulated the expression of genes involved in adipocyte lipid metabolism, decreasing the lipogenic gene (SREBP1) and increasing lipolytic genes (ATGL and HSL). We provide experimental evidence of the health benefits of using (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid obtained from garlic to prevent excessive adipogenesis in obesity.
36
Ding, Menglei, Yu Cheng, Zhen Xu, Ying Lu, Jing Li, Liu Lu, Ming Zong, and Lieying Fan. "Hypoxia Inhibits Osteogenesis and Promotes Adipogenesis of Fibroblast-like Synoviocytes via Upregulation of Leptin in Patients with Rheumatoid Arthritis." Journal of Immunology Research 2022 (December 7, 2022): 1–11. http://dx.doi.org/10.1155/2022/1431399.
Full textAbstract:
Hypoxia is associated with the pathogenesis of rheumatoid arthritis (RA). RA fibroblast-like synoviocytes (FLSs) are able to differentiate into osteoblasts and adipocytes. In this study, we aimed to investigate the role of hypoxia in the osteogenesis or adipogenesis of RA-FLSs. Bioinformatics analysis was performed to profile gene expression in the datasets of GSE21959, GSE32006, and GSE55875, and flow cytometry was performed for FLS characterization, while Alizarin Redand Oil Red O staining for osteogenic or adipogenic differentiation of FLSs, respectively. RNA interference leptin knockdown was used to determine the role of leptin in the osteogenesis and adipogenesis of RA-FLSs, and the expression of osteogenic and adipogenic markers was quantified by RT-qPCR and Western blotting. FLSs exhibited a mesenchymal stem cell (MSC)-like phenotype and we observed a limited self-renewal capacity in RA-FLSs compared to that in MSCs, but it was still greater than osteoarthritis (OA)-FLSs. Hypoxia did not change the RA-FLS MSC-like phenotype but inhibited the osteogenic differentiation and promoted the adipogenic differentiation of RA-FLSs. From the bioinformatics analysis ofGSE21959, GSE32006, and GSE55875 datasets, we found leptin, the only perturbed hypoxia-mediated upregulated gene across the three profiled datasets. Leptin knockdown in RA-FLSs reversed the hypoxia-mediated reduction of osteogenesis and hypoxia-mediated enhancement of adipogenesis by elevated expression of osteogenic markers and reduced expression of adipogenic markers, respectively. Therefore, hypoxia-leptin regulation of the osteogenic and adipogenic differentiation of RA-FLSs advances our understanding of RA pathogenesis, meanwhile also provides opportunities for future therapeutic intervention of RA.
37
Aykul, Senem, Jordan Maust, Vijayalakshmi Thamilselvan, Monique Floer, and Erik Martinez-Hackert. "Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis." International Journal of Molecular Sciences 22, no. 16 (August 6, 2021): 8472. http://dx.doi.org/10.3390/ijms22168472.
Full textAbstract:
Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.
38
Lo Furno, Debora, Adriana Carol Eleonora Graziano, Rosanna Avola, Rosario Giuffrida, Vincenzo Perciavalle, Francesco Bonina, Giuliana Mannino, and Venera Cardile. "ACitrus bergamiaExtract Decreases Adipogenesis and Increases Lipolysis by Modulating PPAR Levels in Mesenchymal Stem Cells from Human Adipose Tissue." PPAR Research 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/4563815.
Full textAbstract:
The aim of this research was to assess the impact of a well-characterized extract fromCitrus bergamiajuice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added withCitrus bergamiafor further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5′-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay.Citrus bergamiaextract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes.Citrus bergamiaextract could be a useful natural product for improving adipose mobilization in obesity-related disorders.
39
Fracaro, Letícia, Alexandra C. Senegaglia, Roberto H. Herai, Amanda Leitolis, Lidiane M. Boldrini-Leite, Carmen L. K. Rebelatto, Paul J. Travers, Paulo R. S. Brofman, and Alejandro Correa. "The Expression Profile of Dental Pulp-Derived Stromal Cells Supports Their Limited Capacity to Differentiate into Adipogenic Cells." International Journal of Molecular Sciences 21, no. 8 (April 15, 2020): 2753. http://dx.doi.org/10.3390/ijms21082753.
Full textAbstract:
Mesenchymal stromal cells (MSCs) can self-renew, differentiate into specialised cells and have different embryonic origins—ectodermal for dental pulp-derived MSCs (DPSCs) and mesodermal for adipose tissue-derived MSCs (ADSCs). Data on DPSCs adipogenic differentiation potential and timing vary, and the lack of molecular and genetic information prompted us to gain a better understanding of DPSCs adipogenic differentiation potential and gene expression profile. While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). To better understand this limitation in adipogenesis, transcriptome analysis in undifferentiated DPSCs was carried out, with the ADSC transcriptome used as a positive control. In total, 14,871 transcripts were common to DPSCs and ADSCs, some were unique (DPSCs: 471, ADSCs: 1032), and 510 were differentially expressed genes. Detailed analyses of overrepresented transcripts showed that DPSCs express genes that inhibit adipogenic differentiation, revealing the possible mechanism for their limited adipogenesis.
40
Zhang, Lei, Carol Paddon, Mark D. Lewis, Fiona Grennan-Jones, and Marian Ludgate. "Gsα signalling suppresses PPARγ2 generation and inhibits 3T3L1 adipogenesis." Journal of Endocrinology 202, no. 2 (May 21, 2009): 207–15. http://dx.doi.org/10.1677/joe-09-0099.
Full textAbstract:
Since TSH receptor (TSHR) expression increases during adipogenesis and signals via cAMP/phospho-cAMP-response element binding protein (CREB), reported to be necessary and sufficient for adipogenesis, we hypothesised that TSHR activation would induce preadipocyte differentiation. Retroviral vectors introduced constitutively active TSHR (TSHR*) into 3T3L1 preadipocytes; despite increased cAMP (RIA) and phospho-CREB (western blot) there was no spontaneous adipogenesis (assessed morphologically, using oil red O and QPCR measurement of adipogenesis markers). We speculated that Gβγ signalling may be inhibitory but failed to induce adipogenesis using activated Gsα (gsp*). Inhibition of phosphodiesterases did not promote adipogenesis in TSHR* or gsp* populations. Furthermore, differentiation induced by adipogenic medium with pioglitazone was reduced in TSHR* and abolished in gsp* expressing 3T3L1 cells. TSHR* and gsp* did not inactivate PPARγ (PPARG as listed in the HUGO database) by phosphorylation but expression of PPARγ1 was reduced and PPARγ2 undetectable in gsp*. FOXO1 phosphorylation (required to inactivate this repressor of adipogenesis) was lowest in gsp* despite the activation of AKT by phosphorylation. PROF is a mediator that facilitates FOXO1 phosphorylation by phospho-Akt. Its transcript levels remained constantly low in the gsp* population. In most measurements, the TSHR* cells were between the gsp* and control 3T3L1 preadipocytes. The enhanced down-regulation of PREF1 (adipogenesis inhibitor) permits retention of some adipogenic potential in the TSHR* population. We conclude that Gsα signalling impedes FOXO1 phosphorylation and thus inhibits PPARγ transcription and the alternative promoter usage required to generate PPARγ2, the fat-specific transcription factor necessary for adipogenesis.
41
Wu, Hang, Taner Pula, Daniel Tews, Ez-Zoubir Amri, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky, and Julian Roos. "microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis." Cells 10, no. 11 (November 17, 2021): 3205. http://dx.doi.org/10.3390/cells10113205.
Full textAbstract:
MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology. Both strands of miR-27a, miR-27a-3p and -5p, were downregulated during the adipogenic differentiation of Simpson–Golabi–Behmel syndrome (SGBS) cells, human multipotent adipose-derived stem cells (hMADS), and human primary adipose-derived stromal cells (hASCs). Using miRNA-mimic transfection, we observed that miR-27a-3p is a crucial regulator of adipogenesis, while miR-27a-5p did not alter the differentiation capacity in SGBS cells. In silico screening predicted lipoprotein lipase (LPL) and peroxisome proliferator activated receptor γ (PPARγ) as potential targets of miR-27a-3p. The downregulation of both genes was verified in vitro, and the interaction of miR-27-3p with target sites in the 3′ UTRs of both genes was confirmed via a miRNA-reporter-gene assay. Here, the knockdown of LPL did not interfere with adipogenic differentiation, while PPARγ knockdown decreased adipogenesis significantly, suggesting that miR-27-3p exerts its inhibitory effect on adipogenesis by repressing PPARγ. Taken together, we identified and validated a crucial role for miR-27a-3p in human adipogenesis played by targeting the essential adipogenic transcription factor PPARγ. Though we confirmed LPL as an additional target of miR-27a-3p, it does not appear to be involved in regulating human adipogenesis. Thereby, our findings call the conclusions drawn from previous studies, which identified LPL as a crucial regulator for murine and human adipogenesis, into question.
42
Petrov, Petar D., Nuria Granados, Carles Chetrit, Daniel Martínez-Puig, Andreu Palou, and M. Luisa Bonet. "Synergistic Effects of a Mixture of Glycosaminoglycans to Inhibit Adipogenesis and Enhance Chondrocyte Features in Multipotent Cells." Cellular Physiology and Biochemistry 37, no. 5 (2015): 1792–806. http://dx.doi.org/10.1159/000438542.
Full textAbstract:
Background/Aims: Multipotent mesenchymal stem cells affect homeostasis of adipose and joint tissues. Factors influencing their differentiation fate are of interest for both obesity and joint problems. We studied the impact of a mixture of glycosaminoglycans (GAGs) (hyaluronic acid: dermatan sulfate 1:0.25, w/w) used in an oral supplement for joint discomfort (Oralvisc™) on the differentiation fate of multipotent cells. Methods: Primary mouse embryo fibroblasts (MEFs) were used as a model system. Post-confluent monolayer MEF cultures non-stimulated or hormonally stimulated to adipogenesis were chronically exposed to the GAGs mixture, its individual components or vehicle. The appearance of lipid laden cells, lipid accumulation and expression of selected genes at the mRNA and protein level was assessed. Results: Exposure to the GAGs mixture synergistically suppressed spontaneous adipogenesis and induced the expression of cartilage extracellular matrix proteins, aggrecan core protein, decorin and cartilage oligomeric matrix protein. Hormonally-induced adipogenesis in the presence of the GAGs mixture resulted in decreased adipogenic differentiation, down-regulation of adipogenic/lipogenic factors and genes for insulin resistance-related adipokines (resistin and retinol binding protein 4), and up-regulation of oxidative metabolism-related genes. Adipogenesis in the presence of dermatan sulfate, the minor component of the mixture, was not impaired but resulted in smaller lipid droplets and the induction of a more complete brown adipocyte-related transcriptional program in the cells in the adipose state. Conclusions: The Oralvisc™ GAGs mixture can tip the adipogenic/chondrogenic fate balance of multipotent cells away from adipogenesis while favoring chondrocyte related gene expression. The mixture and its dermatan sulfate component also have modulatory effects of interest on hormonally-induced adipogenesis and on metabolic and secretory capabilities of adipose cells.
43
Liu, Huimin, Meihong Liu, Zhibo Jin, Sanabil Yaqoob, Mingzhu Zheng, Dan Cai, Jingsheng Liu, and Shaodong Guo. "Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway." Food & Function 10, no. 6 (2019): 3603–14. http://dx.doi.org/10.1039/c9fo00027e.
Full text
44
Lu, Min, and Reigh-Yi Lin. "TSH stimulates adipogenesis in mouse embryonic stem cells." Journal of Endocrinology 196, no. 1 (October 19, 2007): 159–69. http://dx.doi.org/10.1677/joe-07-0452.
Full textAbstract:
Although TSH is the main regulator of thyroid growth and function, TSH binding activity in fat has long been reported. Since the TSH receptor (TSHR) has been detected in both preadipocytes and adipocytes, we hypothesized that it may play a role in adipose differentiation. Here, we use an in vitro model of adipogenesis from mouse embryonic stem (ES) cells to define TSH function. Directed differentiation of ES cells into the adipose lineage can be achieved over a 3-week period. Although adipocyte differentiation is initiated early in the development of cultured ES cells, TSHR up-regulation is precisely correlated with terminal differentiation of those adipocytes. The adipocytes express TSHR on the cell surface and respond to TSH with increased intracellular cAMP production, suggesting the activation of the protein kinase A signaling pathway. To determine whether TSH impacts adipogenesis, we examined how adipocytes responded to TSH at various points during their differentiation from cultured ES cells. We found that TSH greatly increases adipogenesis when added in the presence of adipogenic factors. More importantly, our data suggest that TSH also stimulates adipogenesis in cultured ES cells even in the absence of adipogenic factors. This finding provides the first evidence of TSH being a pro-adipogenic factor that converts ES cells into adipocytes. It further highlights the potential of ES cells as a model system for use in the study of TSH's role in the regulation of physiologically relevant adipose tissue.
45
Zhao, Yurong, Shulin Tang, Ruqin Lin, Ting Zheng, Danyang Li, Xiaoxuan Chen, Jiahui Zhu, Jikai Wen, and Yiqun Deng. "Deoxynivalenol Exposure Suppresses Adipogenesis by Inhibiting the Expression of Peroxisome Proliferator-Activated Receptor Gamma 2 (PPARγ2) in 3T3-L1 Cells." International Journal of Molecular Sciences 21, no. 17 (August 31, 2020): 6300. http://dx.doi.org/10.3390/ijms21176300.
Full textAbstract:
Deoxynivalenol (DON)—a type B trichothecene mycotoxin, mainly produced by the secondary metabolism of Fusarium—has toxic effects on animals and humans. Although DON’s toxicity in many organs including the adrenal glands, thymus, stomach, spleen, and colon has been addressed, its effects on adipocytes have not been investigated. In this study, 3T3-L1 cells were chosen as the cell model and treated with less toxic doses of DON (100 ng/mL) for 7 days. An inhibition of adipogenesis and decrease in triglycerides (TGs) were observed. DON exposure significantly downregulated the expression of PPARγ2 and C/EBPα, along with that of other adipogenic marker genes in 3T3-L1 cells and BALB/c mice. The anti-adipogenesis effect of DON and the downregulation of the expression of adipogenic marker genes were effectively reversed by PPARγ2 overexpression. The repression of PPARγ2′s expression is the pivotal event during DON exposure regarding adipogenesis. DON exposure specifically decreased the di-/trimethylation levels of Histone 3 at lysine 4 in 3T3-L1 cells, therefore weakening the enrichment of H3K4me2 and H3K4me3 at the Pparγ2 promoter and suppressing its expression. Conclusively, DON exposure inhibited PPARγ2 expression via decreasing H3K4 methylation, downregulated the expression of PPARγ2-regulated adipogenic marker genes, and consequently suppressed the intermediate and late stages of adipogenesis. Our results broaden the current understanding of DON’s toxic effects and provide a reference for addressing the toxicological mechanism of DON’s interference with lipid homeostasis.
46
Xiong, Yan, Qing Xu, Sen Lin, Yong Wang, Yaqiu Lin, and Jiangjiang Zhu. "Knockdown of LXRα Inhibits Goat Intramuscular Preadipocyte Differentiation." International Journal of Molecular Sciences 19, no. 10 (October 5, 2018): 3037. http://dx.doi.org/10.3390/ijms19103037.
Full textAbstract:
Goat intramuscular fat (IMF) content is mainly determined by the processes of intramuscular preadipocytes adipogenic differentiation and mature adipocyte lipid accumulation. However, the underlying regulators of these biological processes remain largely unknown. Here, we report that the expression of Liver X receptor alpha (LXRα) reaches a peak at early stage and then gradually decreases during goat intramuscular adipogenesis. Knockdown of LXRα mediated by two independent siRNAs significantly inhibits intramuscular adipocytes lipid accumulation and upregulates preadipocytes marker- preadipocyte factor 1 (pref1) expression. Consistently, siRNA treatments robustly decrease mRNA level of adipogenic related genes, including CCAAT enhancer binding protein alpha (Cebpα), Peroxisome proliferator activated receptor gamma (Pparg), Sterol regulatory element binding protein isoform 1c (Srebp1c), Fatty acids binding protein (aP2) and Lipoprotein lipase (Lpl). Next, adenovirus overexpression of LXRα does not affect intramuscular adipocytes adipogenesis manifested by Oil Red O signal measurement and adipogenic specific genes detection. Mechanically, we found that both CCAAT enhancer binding protein beta (Cebpβ) and Kruppel like factor 8 (Klf8) are potential targets of LXRα, indicated by having putative binding sites of LXRα at the promoter of these genes and similar expression pattern during adipogenesis comparing to LXRα. Importantly, mRNA levels of Cebpβ and Klf8 are downregulated significantly in goat LXRα knockdown intramuscular adipocyte. These results demonstrate that loss function of LXRα inhibits intramuscular adipogenesis possibly through down-regulation of Cebpβ and Klf8. Our research will provide new insights into mechanical regulation of goat IMF deposition.
47
Ohlstein, Jason F., Amy L. Strong, John A. McLachlan, Jeffrey M. Gimble, Matthew E. Burow, and Bruce A. Bunnell. "Bisphenol A enhances adipogenic differentiation of human adipose stromal/stem cells." Journal of Molecular Endocrinology 53, no. 3 (August 20, 2014): 345–53. http://dx.doi.org/10.1530/jme-14-0052.
Full textAbstract:
Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM–10 μM). The extent of adipogenic differentiation in the ASCs was assessed by staining with Oil Red O to visualize adipogenic differentiation and then quantified by extraction and optical density measurement of the retained dye. BPA significantly enhanced adipogenesis at a concentration of 1 μM after 21 days of culture. Additionally, we found that BPA increased transcription of the estrogen receptor (ER (ESR1)) and that treatment with the ER antagonist ICI 182 780, blocked the effects of BPA, indicating that BPA may act via an ER-mediated pathway. The results of molecular analyses indicated that the expression of the adipogenesis-associated genes dual leucine zipper-bearing kinase (DLK (MAP3K12)), IGF1, CCAAT/enhancer-binding protein alpha (C/EBPα (CEBPA)), peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), and lipoprotein lipase (LPL) was temporally accelerated and increased by BPA. In summary, these results indicate that BPA significantly enhances adipogenesis in ASCs through an ER-mediated pathway at physiologically relevant concentrations.
48
Sen, Buer, Zhihui Xie, Natasha Case, Meiyun Ma, Clinton Rubin, and Janet Rubin. "Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal." Endocrinology 149, no. 12 (August 7, 2008): 6065–75. http://dx.doi.org/10.1210/en.2008-0687.
Full textAbstract:
The ability of exercise to decrease fat mass and increase bone mass may occur through mechanical biasing of mesenchymal stem cells (MSCs) away from adipogenesis and toward osteoblastogenesis. C3H10T1/2 MSCs cultured in highly adipogenic medium express peroxisome proliferator-activated receptor γ and adiponectin mRNA and protein, and accumulate intracellular lipid. Mechanical strain applied for 6 h daily inhibited expression of peroxisome proliferator-activated receptor γ and adiponectin mRNA by up to 35 and 50%, respectively, after 5 d. A decrease in active and total β-catenin levels during adipogenic differentiation was entirely prevented by daily application of mechanical strain; furthermore, strain induced β-catenin nuclear translocation. Inhibition of glycogen synthase kinase-3β by lithium chloride or SB415286 also prevented adipogenesis, suggesting that preservation of β-catenin levels was important to strain inhibition of adipogenesis. Indeed, mechanical strain inactivated glycogen synthase kinase-3β, which was preceded by Akt activation, indicating that strain transmits antiadipogenic signals through this pathway. Cells grown under adipogenic conditions showed no increase in osteogenic markers runt-related transcription factor (Runx) 2 and osterix (Osx); subsequent addition of bone morphogenetic protein 2 for 2 d increased Runx2 but not Osx expression in unstrained cultures. When cultures were strained for 5 d before bone morphogenetic protein 2 addition, Runx2 mRNA increased more than in unstrained cultures, and Osx expression more than doubled. As such, mechanical strain enhanced MSC potential to enter the osteoblast lineage despite exposure to adipogenic conditions. Our results indicate that MSC commitment to adipogenesis can be suppressed by mechanical signals, allowing other signals to promote osteoblastogenesis. These data suggest that positive effects of exercise on both fat and bone may occur during mesenchymal lineage selection.
49
Liu, Bin, Dinghui Wang, Tianhua Xiong, Yajie Liu, Xiaodong Jing, Jianlin Du, and Qiang She. "Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes." Stem Cells International 2021 (April 9, 2021): 1–12. http://dx.doi.org/10.1155/2021/8859071.
Full textAbstract:
Background. The role of Notch signaling pathway in the differentiation of epicardial progenitor cells (EPCs) into adipocytes is unclear. The objective is to investigate the effects of Notch signaling on the differentiation of EPCs into adipocytes. Methods. Frozen sections of C57BL/6J mouse hearts were used to observe epicardial adipose tissue (EAT), and genetic lineage methods were used to trace EPCs. EPCs were cultured in adipogenic induction medium with Notch ligand jagged-1 or γ-secretase inhibitor DAPT. The adipocyte markers, Notch signaling, and adipogenesis transcription factors were determined. Results. There was EAT located at the atrial–ventricular groove in mouse. By using genetic lineage tracing methods, we found that EPCs were a source of epicardial adipocytes. EPCs had lipid droplet accumulation, and the expression of adipocyte markers FABP-4 and perilipin-1 was upregulated under adipogenic induction. Activating the Notch signaling with jagged-1 attenuated the adipogenic differentiation of EPCs and downregulated the key adipogenesis transcription factor peroxisome proliferator activated receptor-γ (PPAR-γ), while inhibiting the signaling promoted adipogenic differentiation and upregulated PPAR-γ. When blocking PPAR-γ, the role of Notch signaling in promoting adipogenic differentiation was inhibited. Conclusions. EPCs are a source of epicardial adipocytes. Downregulation of the Notch signaling pathway promotes the differentiation of EPCs into adipocytes via PPAR-γ.
50
Wang, Yan, Judith C. W. Mak, Mary Y. K. Lee, Aimin Xu, and Mary S. M. Ip. "Low-Frequency Intermittent Hypoxia Promotes Subcutaneous Adipogenic Differentiation." Oxidative Medicine and Cellular Longevity 2018 (March 12, 2018): 1–13. http://dx.doi.org/10.1155/2018/4501757.
Full textAbstract:
Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is associated with obesity and metabolic disorders. The mass and function of adipose tissue are largely dependent on adipogenesis. The impact of low-frequency IH on adipogenesis is unknown. Sprague-Dawley rats were subjected to IH (4 min for 10% O2 and 2 min for 21% O2) or intermittent normoxia (IN) for 6 weeks. The degree of adipogenic differentiation was evaluated by adipogenic transcriptional factors, adipocyte-specific proteins, and oily droplet production in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Upregulation of proadipogenic markers (CEBPα, PPARγ, and FABP4) and downregulation of antiadipogenic markers CHOP in line with smaller size of adipocytes were found in IH-exposed SAT. In vitro experiments using human preadipocytes (HPAs) of subcutaneous lineage during differentiation phase, subjected to IH (1% O2 for 10 min and 21% O2 for 5 min; 5% CO2) or IN treatment, were done to investigate the insulin-like growth factor 1 receptor (IGF-1R)/Akt pathway in adipogenesis. IH promoted the accumulation of oily droplets and adipogenesis-associated markers. IGF-1R kinase inhibitor NVP-AEW541 attenuated the proadipogenic role in IH-exposed HPAs. In summary, relatively low frequency of IH may enhance adipogenesis preferentially in SAT.