Epigenetic imprinting of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes [ChIP-seq]
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ORGANISM(S): Rattus norvegicus
PROVIDER: GSE255335 | GEO | 2024/06/06
REPOSITORIES: GEO
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Project description:Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes. The aim of this study was to investigate the effect of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from mice fed a high-fat sucrose (HFS) diet exhibited reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than those from the control group (C). The results showed that ASCs from mice fed the HFS diet had reduced adipogenic capacity. Mitochondrial analysis showed increased mitochondrial activity in undifferentiated ASC-HFS, but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 acetylation profile of ASCs in genes related to adipogenesis, mitochondrial function, inflammatory response and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations in genes related to inflammatory response and immunomodulation. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. This study demonstrates that HFS diet induces profound epigenetic and transcriptomic changes in ASCs, leading to impaired differentiation and dysfunctional adipocyte formation.
2024-06-06 | GSE255334 | GEO
Project description:We isolated adipose-derived mesenchymal stem cells (ASCs) from the lymphedema adipose tissue from liposuction specimens of 10 patients with malignancy-related extremity lymphedema, and we used adipose tissue from the normal upper abdomen of the same patients as control tissue. We compared the proliferation and adipogenic differentiation capacity between the two kinds of ASCs, and we explored the transcriptomic differences between them. We found that lymphedema-associated ASCs had more rapid proliferation and a higher adipogenic differentiation capacity. CDK1 inhibitors could return the abnormal biological characteristics of these cells to normal phenotype, suggesting that CDK1 is a key driver of proliferation and adipogenic differentiation in these cells, which might expound the accumulation of adipose tissue extensively observed in secondary lymphedema, indicating the CDK1 may be a potential target for lymphedema therapy. On the other hand, our finding showed that ASCs from lymphedema adipose tissues have higher immunosuppressive effect, and the inhibition of up-regulated cytokine CHI3L1 may be clinically beneficial. In summary, explore the underlying mechanisms of fat deposition in lymphedema may provide powerful strategies for the treatment of lymphedema.
2019-06-19 | GSE132936 | GEO
Project description:Adipose stem cells (ASCs) and adipocytes play a crucial role in maintaining energy balance. We aim to examine the temporal relationship between gene expression and histone modification transitions during in vitro differentiation of human ASCs into adipocytes. Here, we examine by RNAseq proliferating ASCs (Day -2 prior to adipogenic induction), confluent ASCs (Day 0, adipogenic induction), pre-adipocytes (Day 3) and maturing adipocytes (Day 9). We find 1060, 5452 and 2216 genes differentially expressed between D-2/D0, D0/D3 and D3/D9 respectively. We identify gene clusters with distinct and dynamic expression patterns. In particular, adipogenic induction is marked by temporal waves of gene induction and downregulation. We report two types of transcriptional waves: (i) those showing transient induction or inactivation at D0, D3 or D9, and involved in sensory perception and immune response functions; and (ii) those showing long-lived induction or repression at these time points. Our data reveal a dynamic network of gene regulation during adipogenesis, involving signaling, immune and developmental processes. We identify 15 unique epigenetic states using Hidden Markov Modeling which reflects an epigenetically highly organised genome showing enhancer states are commonly consecutive. A heatmap for the abundance of epigenetic states for the expression clusters reveals a link between expression and epigenetic marking of the state suggesting an increase in the number of number of chromatin states with increase in expression. Our data point to a model of increased epigenetic complexity associated with gene expression. Examination of expression of profiles of ASCs across differentiation
2014-12-10 | E-GEOD-60237 | biostudies-arrayexpress
Project description:Adipose stem cells (ASCs) and adipocytes play a crucial role in maintaining energy balance. We aim to examine the temporal relationship between gene expression and histone modification transitions during in vitro differentiation of human ASCs into adipocytes. Here, we examine by RNAseq proliferating ASCs (Day -2 prior to adipogenic induction), confluent ASCs (Day 0, adipogenic induction), pre-adipocytes (Day 3) and maturing adipocytes (Day 9). We find 1060, 5452 and 2216 genes differentially expressed between D-2/D0, D0/D3 and D3/D9 respectively. We identify gene clusters with distinct and dynamic expression patterns. In particular, adipogenic induction is marked by temporal waves of gene induction and downregulation. We report two types of transcriptional waves: (i) those showing transient induction or inactivation at D0, D3 or D9, and involved in sensory perception and immune response functions; and (ii) those showing long-lived induction or repression at these time points. Our data reveal a dynamic network of gene regulation during adipogenesis, involving signaling, immune and developmental processes. We identify 15 unique epigenetic states using Hidden Markov Modeling which reflects an epigenetically highly organised genome showing enhancer states are commonly consecutive. A heatmap for the abundance of epigenetic states for the expression clusters reveals a link between expression and epigenetic marking of the state suggesting an increase in the number of number of chromatin states with increase in expression. Our data point to a model of increased epigenetic complexity associated with gene expression.
2014-12-10 | GSE60237 | GEO
Project description:Background. Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. LIM Domain Only 3 (LMO3) plays a crucial role in adipogenesis modulating the key adipogenic master switch PPARγ in human, but not mouse, visceral adipose progenitors; however, despite high expression in mature adipocytes, its function in these cells is currently unknown. Aims/Hypothesis. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Methods. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain- or loss of LMO3 expression, respectively.Results. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. Lmo3 expression in eWAT significantly improved glucose clearance and insulin sensitivity in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, Lmo3 expression in 3T3-L1 adipocytes increased insulin-stimulated GLUT4 translocation and glucose uptake as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. On a molecular level, LMO3 augmented PPARg activity, oxidative mitochondrial gene expression, which depended on and the expression of the PPARg co-activator Ncoa1, which was required for LMO3 effects on mitochondria and glucose uptake. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. Conclusions. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose tolerance, insulin sensitivity and adiponectin secretion. Together with increased PPARγ activity, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity.
2021-08-24 | GSE155781 | GEO
Project description:To better understand the scale of gene expression changes that occur during the formation of mature adipocytes from preadipocytes, we compared and characterised the transcriptome profile of mesenchymal stromal cells derived from human adipose tissue, otherwise known as adipose-derived stromal cells (ASCs), undergoing adipocyte differentiation on day 1, 7, 14 and 21 (representing the early to late stage process of adipogenesis). Microarray technique was systematically employed to study gene expression in adipose-derived stromal cells during adipogenic differentiation over a 21 day period to identify genes that are important in driving adipogenesis in humans. We have undertaken an in-depth transcriptome analysis of adipogenesis in human adipose-derived stromal cells (ASCs) induced to differentiate into adipocytes in vitro. Genes were differentially expressed on days 1, 7, 14 and 21 post-induction and numbered 128, 218, 253 and 240 respectively. Up-regulated genes were associated with neural and blood vessel development, leukocyte migration, and tumor growth, invasion and metastasis. They also shared common pathways with certain obesity-related pathophysiological conditions. Down-regulated genes were associated with osteogenesis and the immune response. KLF15, LMO3, FOXO1 and ZBTB16 transcription factors were up-regulated throughout the differentiation process. CEBPA, PPARG, ZNF117, MLXIPL, MMP3 and RORB were up-regulated only on days 14 - 21, which coincides with the maturation of adipocytes and could possibly serve as candidates for controlling fat accumulation and the size of mature adipocytes. We identified genes that were up-regulated only on day 1 - 7 and day 14 - 21 that could serve as potential early and late-stage differentiation markers. This study reveals potential markers for the different stages in ASC adipogenic differentiation which could serve as good candidates to combat obesity and further link the biology of fat cell formation to the co-morbidities of obesity.
2016-12-01 | GSE77532 | GEO
Project description:Brown adipose tissue (BAT) holds therapeutic potential for obesity and metabolic syndrome via increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generation of brown and white preadipocyte clones from human neck fat and characterized their adipogenic differentiation and thermogenic function. Combining a UCP1 reporter system and gene expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of mature adipocytes. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes by CRISPRs markedly abolished the high level of UCP1 in mature brown adipocytes. Finally, we showed the ability to prospectively isolate adipose progenitors with great thermogenic potential. These data provide new insights into the cellular heterogeneity in human fat and offer clinically relevant gene targets that mark thermogenically competent preadipocytes. Highly adipogenic clonal white and brown cell lines
2015-06-15 | E-GEOD-68544 | biostudies-arrayexpress
Project description:Aims/Hypothesis. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Methods. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain- or loss of LMO3 expression, respectively. Results. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. Lmo3 expression in eWAT significantly improved glucose clearance and insulin sensitivity in diet-induced obesity, paralleled by increased serum adiponectin. On a molecular level, LMO3 expression in eWAT increased pathways indicative of adipogenesis and PPARg signaling as well as mitochondrial activity, paralleled by a suppression of adipose tissue fibrosis. In vitro, Lmo3 expression in 3T3-L1 adipocytes increased insulin-stimulated GLUT4 translocation and glucose uptake as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. LMO3 overexpression promoted, while silencing of LMO3 suppressed, mitochondrial oxidative capacity in human mature adipocytes. Conclusions. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose tolerance, insulin sensitivity and adiponectin secretion. Together with increased PPARγ activity, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity.
2021-08-24 | GSE139162 | GEO
Project description:Aims/Hypothesis. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Methods. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain- or loss of LMO3 expression, respectively. Results. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. Lmo3 expression in eWAT significantly improved glucose clearance and insulin sensitivity in diet-induced obesity, paralleled by increased serum adiponectin. On a molecular level, LMO3 expression in eWAT increased pathways indicative of adipogenesis and PPARg signaling as well as mitochondrial activity, paralleled by a suppression of adipose tissue fibrosis. In vitro, Lmo3 expression in 3T3-L1 adipocytes increased insulin-stimulated GLUT4 translocation and glucose uptake as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. LMO3 overexpression promoted, while silencing of LMO3 suppressed, mitochondrial oxidative capacity in human mature adipocytes. Conclusions. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose tolerance, insulin sensitivity and adiponectin secretion. Together with increased PPARγ activity, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity.
2021-08-24 | GSE139155 | GEO
Project description:The healthy growth of adipose tissue depends on the capacity of progenitor cells to undergo denovo adipogenesis. However, the cellular hierarchy and mechanisms governing adipocyteprogenitor differentiation are incompletely understood. Here, we identify a lineage hierarchy25 consisting of distinct mesenchymal cell types present in mouse and human adipose tissue. Cellsmarked by Dpp4 expression are highly proliferative, multipotent progenitors that give rise toIcam1+ committed pre-adipocytes and a related adipogenic population marked by Clec11a andCd142 expression. TGFβ maintains DPP4+ cell identity and inhibits adipogenic commitment ofDPP4+ and CD142+ cells. Intriguingly, DPP4+ progenitors reside in the reticular interstitium that30 envelope many organs including adipose depots. Altogether, this study defines the adipose lineagehierarchy and identifies a new anatomical niche for multipotent mesenchymal progenitors.
2019-05-01 | GSE128891 | GEO