Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [microarrays]
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ABSTRACT: To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals
Project description:To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals
Project description:To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals
Project description:To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals
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.
Project description:Using RNA isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples obtained from control and class I, II and III obese patients undergoing inguinal hernia repair and laparoscopic cholecystectomy, we compared the gene expression profiles between SAT and VAT using microarrays and validated the findings by real-time quantitative PCR. Two-condition experiment, SAT vs. VAT tissue. Biological replicates: 8 SAT replicates, 8 VAT replicates.
Project description:Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH. We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART. We enrolled PWH on long-term ART with a spectrum of metabolic health.We enrolled PWH on long-term ART with a spectrum of metabolic health. Ninety-two participants underwent SAT biopsy for bulk RNA sequencing and 43 had single-cell RNA sequencing. Computed tomography quantified VAT volume and insulin resistance was calculated using HOMA2-IR. VAT volume was associated with HOMA2-IR (p<0.001). Higher proportions of SAT intermediate macrophages (IMs), myofibroblasts, and MYOC+ fibroblasts were associated with greater VAT volume using partial Spearman’s correlation adjusting for age, sex, and body mass index (r =0.34-0.49, p<0.05 for all). Whole SAT transcriptomics showed PWH with greater VAT volume have increased expression of extracellular matrix (ECM)- and inflammation-associated genes, and reduced expression of lipolysis- and fatty acid metabolism-associated genes. In PWH, greater VAT volume is associated with higher proportion of SAT IMs and fibroblasts, and a SAT ECM and inflammatory transcriptome, which is similar to findings in HIV-negative persons with obesity. These data identify SAT cell-type specific changes associated with VAT volume in PWH that could underlie the high rates of cardiometabolic diseases in PWH, though additional longitudinal studies are needed to define directionality and mechanisms.
Project description:Using RNA isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples obtained from control and class I, II and III obese patients undergoing inguinal hernia repair and laparoscopic cholecystectomy, we compared the gene expression profiles between SAT and VAT using microarrays and validated the findings by real-time quantitative PCR.
Project description:To investigate the proteomic profiles of paired subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples, as well as their correlations with clinical traits in severely obese patients, and to identify potential serum protein markers associated with tissue expression or metabolic states.
Project description:To investigate the proteomic profiles of paired subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples, as well as their correlations with clinical traits in severely obese patients, and to identify potential serum protein markers associated with tissue expression or metabolic states.