Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone receptor [RNA-seq]

ABSTRACT: Adipocyte dysfunctuon exacerbates obesity, yet the onset of adipocyte dysfunction is still unclear. Here, we employed RNA-seq and ATAC-seq on visceral adipose tissue from individuals with obesity or normal weight.Our research identified differentially expressed genes (DEGs) of VAT from individuals with normal wight or obesity enriched in pathways related to adipocyte metabolic function, thyroid hormone receptor binding sites were discovered in the accessible chromatin regions of these DEGs, including STAT5B. Motif enrichment, CHIP assay and in vitro cell experiments confirmed the decreased activation of STAT5B by triiodothyronine (T3) through binding with thyroid hormone receptor alpha (THRa) in obesity. In addition, RNA interference revealed STAT5B as a key transcription factor in maintaining the metabolic function of VAT. In conclusion, the impaired metabolic function of VAT is associated with altered chromatin accessibility to thyroid hormone (TH) in obesity. STAT5B is a key transcription factor at the core of the disrupted thyroid-adipose signaling and might be a promising target to improve obesity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286532 | GEO | 2025/05/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Visceral adipocyte metabolic dysfunction in obesity related to altered chromatin accessibility to thyroid hormone receptor [ATAC-seq]

Project description:Adipocyte dysfunctuon exacerbates obesity, yet the onset of adipocyte dysfunction is still unclear. Here, we employed RNA-seq and ATAC-seq on visceral adipose tissue from individuals with obesity or normal weight.Our research identified differentially expressed genes (DEGs) of VAT from individuals with normal wight or obesity enriched in pathways related to adipocyte metabolic function, thyroid hormone receptor binding sites were discovered in the accessible chromatin regions of these DEGs, including STAT5B. Motif enrichment, CHIP assay and in vitro cell experiments confirmed the decreased activation of STAT5B by triiodothyronine (T3) through binding with thyroid hormone receptor alpha (THRa) in obesity. In addition, RNA interference revealed STAT5B as a key transcription factor in maintaining the metabolic function of VAT. In conclusion, the impaired metabolic function of VAT is associated with altered chromatin accessibility to thyroid hormone (TH) in obesity. STAT5B is a key transcription factor at the core of the disrupted thyroid-adipose signaling and might be a promising target to improve obesity.

2025-05-19 | GSE286534 | GEO

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue.

Project description:Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

2024-04-23 | PXD048506 | Pride

A dynamic subcutaneous adipose transcriptome of human insulin resistance identifies a molecular predisposition shared with visceral adipose tissue

Project description:Subcutaneous adipose tissue (SAT) is classically viewed as a metabolic buffer for lipid deposition during positive caloric balance, while visceral adipose tissue (VAT) is viewed as the dominant contributor and prime mediator of insulin resistance (IR) and cardiometabolic disease risk. Nevertheless, a growing body of data suggests that similar morphologic and molecular changes may occur in SAT as in VAT during obesity. In addition, while pro-inflammatory immune changes within adipose are thought to drive IR there is increasing data implicating a role for adipocytes and stromal populations especially in humans. Here, we identified a transcriptional landscape of IR in SAT of 220 humans across the spectrum of obesity and IR states, highlighting a broad range of metabolic pathways central to IR. Using single cell and nucleus deconvolution and statistical learning techniques, we identified a 35-gene signature that (1) achieved high predictive accuracy for homeostatic model of IR (HOMA-IR) across BMI; (2) was expressed across a variety of non-immune cell populations (most prominently adipocytes and adipocyte stem and precursor cells [ASPCs]), with primarily “protective” IR associations for adipocyte transcripts and “deleterious” associations for macrophage transcripts; (3) displayed a high concordance between SAT and VAT (greater than non-IR associated genes). Multiple SAT genes exhibited dynamic expression 5-years after weight loss surgery and with insulin stimulation. Finally, using available expression quantitative trait loci in SAT and/or VAT, we demonstrate similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI, suggesting underlying similarities in genetic determinants of IR between adipose depots. These results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and that is shared with VAT, nuancing the current VAT-centric concept of IR in humans.

2024-10-19 | GSE245948 | GEO

Removal of visceral adipose tissue prevents obesity-induced multi-organ insulin resistance, dyslipidemia, and NAFLD in mice

Project description:Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. It has been postulated that accumulation of visceral adipose tissue (VAT) causes obesity-induced insulin resistance. The major purpose of this study was to test hypothesis that prophylactic VAT removal prevents the development of obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance, dyslipidemia, and NAFLD. Accordingly, we surgically removed epididymal VAT from adult C57BL/6J mice and then evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following feeding of chronic high-fat diet (HFD). We found that VAT removal prevented HFD-induced insulin resistance and markedly increased AKT-mediated insulin signaling in subcutaneous adipose tissue (SAT), liver, and skeletal muscle. VAT removal improved plasma lipid profiling and prevented obesity-induced NAFLD. In addition, VAT removal significantly increased circulating level of adiponectin, a key insulin-sensitizing adipokine, whereas it decreased interleukin-6, a pro-inflammatory adipokine. Data obtained from RNA-sequencing suggest that VAT removal prevents obesity-induced oxidative stress and inflammation in liver and SAT respectively. These findings demonstrate the causative role of VAT in the development of obesity and related systemic metabolic complications, such as insulin resistance, dyslipidemia, and NAFLD.

2021-04-01 | GSE157798 | GEO

A long-term high fat diet induces differential gene expression changes in spatially distinct adipose tissues.

Project description:The accumulation of visceral adipose tissue (VAT) is strongly associated with cardiovascular disease and diabetes. In contrast, individuals with increased subcutaneous adipose tissue (SAT) without corresponding increases in VAT are associated with a metabolic healthy obese phenotype. These observations implicate dysfunctional VAT as a driver of disease processes, warranting investigation into obesity-induced alterations of distinct adipose depots. To determine the effects of obesity on adipose gene expression, mice were fed either a high fat or normal laboratory diet for 12-14 months. Mesenteric VAT and hindlimb SAT were isolated from four lean controls and four obese mice for bulk RNA- sequencing. AT from lean controls served as a reference to obesity-induced changes. The long-term high fat diet induced the expression of 169 and 814 unique genes in SAT and VAT, respectively. SAT from obese mice exhibited a total of 308 differentially expressed genes (164 upregulated, 144 downregulated). VAT from obese mice exhibited 690 differentially expressed genes (262 genes upregulated, 428 downregulated). KEGG pathway and GO analyses revealed that metabolic pathways were upregulated in SAT vs. downregulated in VAT while inflammatory signaling was upregulated in VAT. We next determined common genes that were differentially regulated between SAT and VAT in response to obesity and identified four genes that exhibited this profile: elovl6 and kcnj15 were upregulated in SAT/downregulated in VAT while trdn and hspb7 were downregulated in SAT/ upregulated in VAT. We propose that these genes in particular should be further pursued to determine their roles in SAT vs. VAT with obesity.

2024-06-12 | GSE269663 | GEO

The impact of Srebf2 deletion on the transcriptional phenotype of visceral adipose tissue (VAT) regulatory T (Treg) cells

Project description:Regulatory T (Treg) cells are highly enriched in the visceral adipose tissue (VAT) to maintain metabolic homeostasis, but they are lost during obesity. VAT Treg cells exhibit enhanced Srebf2-dependent cholesterol metabolism compared lymphoid tissue Tregs at steady state, but this metabolic pathway is disrupted during obesity. Therefore, the goal of this study is to determine the impact of Treg-specific Srebf2 deletion on the transcriptional phenotype of bulk Foxp3+ VAT or splenic Tregs.

2025-01-10 | GSE243021 | GEO

Obesity disrupts cellular cholesterol homeostasis to inhibit the homeostatic clonal expansion of ST2hi VAT Treg cells

Project description:Regulatory T (Treg) cells are highly enriched in the visceral adipose tissue (VAT) to maintain metabolic homeostasis, but they are lost during obesity. Currently, how VAT Treg cells rewire cellular metabolism to support their homeostatic clonal expansion, and whether this process is disrupted in obesity, is unclear. Here, we found that cholesterol metabolism was uniquely upregulated in VAT-, but not other non-lymphoid-tissue Treg cells. Disrupting cholesterol homeostasis (CH) by Treg-specific deletion of Srebf2 led to a specific loss of VAT Treg cells and enhanced obesity-induced systemic metabolic dysfunction. Mechanistically, Srebf2-mediated CH potentiated strong TCR signaling, which specifically promoted the clonal expansion of ST2hi, but not other, VAT Treg subsets. However, long-term high-fat-diet feeding disrupted VAT Treg CH and impaired ST2hi VAT Treg clonal expansion. Restoring Treg CH rescued VAT Treg accumulation in obese mice, suggesting CH modulation could be a potential option for Treg-targeted therapies in obesity-associated metabolic diseases.

2025-01-10 | GSE243563 | GEO

Human subcutaneous adipose tissue and perithyroid adipose tissue gene expression

Project description:Different human adipose tissue depots may have functional differences. Subcutaneous human adipose tissue has been extensively studied, but less is known about other depots. Perithyroid (PT) adipose tissue contains not only white adipocytes but also brown adipocytes. The aim of this study was to compare the expression of brown adipocyte containing perithyroid adipose tissue with s.c. adipose tissue.role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders. Expression analysis of paired biopsies from s.c and perithyriod (PT) adipose tissue from nine subjects undergoing surgery in the thyroid region.

2013-01-22 | E-GEOD-27657 | biostudies-arrayexpress

Proteome analysis of human visceral and subcutaneous adipocytes identifies altered metabolic control points

Project description:Adipose tissue is a primary regulator of energy balance and metabolism. The distribution of adipose tissue depots is of clinical interest because the accumulation of upper-body subcutaneous (ASAT) and visceral adipose tissue (VAT) is associated with cardiometabolic diseases, whereas lower-body gluteal-femoral adipose tissue (GFAT) appears to be protective. There is heterogeneity in the morphological and metabolic traits of adipocytes obtained from different regions of the body, but detailed knowledge of the constituent proteins in each depot is lacking. Here, we determined the human adipocyte proteome from ASAT, VAT and GFAT using high-resolution SWATH mass spectrometry proteomics.

2021-04-19 | PXD018314 | Pride

Deep subcutaneous adipose tissue (dSAT) vs. superficial subcutaneous adipose (sSAT)

Project description:In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly linked to metabolic and cardiovascular complications of obesity. We recently showed that the severity of liver non-alcoholic histopathology in obese subjects increased with the amounts of macrophages in visceral adipose tissue (VAT), while no relation was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into superficial (sSAT) and deep (dSAT) layers. The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alteration in obesity. Total RNA was isolated from two different strata of human adipose tissue of 8 subjects.

2011-08-31 | E-GEOD-30133 | biostudies-arrayexpress