Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes

Bradford, Stephen; Nair, Shalima S.; Statham, Aaron L.; Dijk, Susan J. van; Peters, Timothy J.; Anwar, Firoz; French, Hugh J.; Martels, Julius Z. H. von; Sutcliffe, Brodie; Maddugoda, Madhavi P.; Peranec, Michelle; Varinli, Hilal; Arnoldy, Rosanna; Buckley, Michael; Ross, Jason P.; Zotenko, Elena; Song, Jenny Z.; Stirzaker, Clare; Bauer, Denis C.; Qu, Wenjia; Swarbrick, Michael M.; Lutgers, Helen L.; Lord, Reginald V.; Samaras, Katherine; Molloy, Peter L.; Clark, Susan J.

doi:10.1038/s41598-019-45777-w

Cited by 26 publications

(31 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genes related to adipocyte metabolism (proliferation, differentiation, lipid turnover, etc. ), adipokine secretion, and ion channels and cell signaling are also differentially expressed in sWAT and vWAT, according to transcriptome studies [ 34 – 36 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

2020

View full text Add to dashboard Cite

In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

2020

View full text Add to dashboard Cite

show abstract

“…Although this is the first study to conduct deep proteomic analysis of regional isolated adipocytes, others have previously profiled the transcriptome and proteome of whole VAT and ASAT, which consists of a mix of $50% adipocytes and $50% of other cell types residing in the stromal vascular fraction. Based on the upregulation of inflammatory genes in VAT when compared with ASAT and the upregulation of genes involved in lipid metabolism and insulin signaling in ASAT when compared with VAT, previous transcriptome studies indicate that VAT is associated with cardiovascular diseases and ASAT is associated with improved systemic lipid homeostasis (25)(26)(27). Developmental genes are differentially regulated between ASAT and GFAT (71)(72)(73), and these previous studies highlight that the ASAT gene expression may be similar to VAT.…”

Section: Discussionmentioning

confidence: 97%

“…Another study showed that the proteins involved in cell structure and energy metabolism are differentially expressed between ASAT and GFAT in morbidly obese women (31). Transcriptome analyses of isolated adipocytes are also limited, with differential regulation in genes involved in insulin signaling, lipid metabolism, adipogenic differentiation, angiogenesis, and development reported between adipocytes obtained from VAT and ASAT (25). Another study showed that the transcriptome of adipocytes derived from GFAT is overrepresented with glucose and lipid metabolic pathways compared with adipocytes from ASAT (74).…”

Section: Discussionmentioning

confidence: 99%

“…The molecular regulation within adipocytes directs the production and degradation of proteins that invariably control cellular functions (24). Others have profiled the whole transcriptome of human adipose tissues obtained from visceral and subcutaneous locations (25)(26)(27), which indicated that the genes involved in cellular and embryonic development, connective tissues disorders, cell morphology, lipid droplet formation and mobilization, and angiogenesis-related pathways were differentially regulated between these adipose sites. Cross-sectional analysis of the proteomes from whole VAT and ASAT (28)(29)(30) indicates that proteins associated with glucose and lipid metabolism, lipid transport, response to stress and inflammation, and nuclear receptor activation pathways were differentially regulated, whereas a recent study (31) reported few differences between the ASAT and GFAT proteomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points

Raajendiran

Souza

Ooi

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

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 morphology and metabolism 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. We quantified 4220 proteins in adipocytes, and 2329 proteins were expressed in all three adipose depots. Comparative analysis revealed significant differences between adipocytes from different regions (6 and 8% when comparing VAT vs.ASAT and GFAT, 3% when comparing the subcutaneous adipose tissue depots, ASAT and GFAT), with marked differences in proteins that regulate metabolic functions. The VAT adipocyte proteome was overrepresented with proteins of glycolysis, lipogenesis, oxidative stress and mitochondrial dysfunction. The GFAT adipocyte proteome predicted activation of PPARα, fatty acid and BCAA oxidation, enhanced TCA cycle flux and oxidative phosphorylation, which was supported by metabolomic data obtained from adipocytes. Together, this proteomic analysis provides an important resource and novel insights that enhance the understanding of metabolic heterogeneity in the regional adipocytes of humans.

show abstract

“…Metabolically unhealthy obesity is dominated by intra- and extra-abdominal WAT characterized by insulin resistance and inflammation and correlates more to visceral abdominal WAT (vWAT) than to subcutaneous WAT (sWAT) [ 36 ]. According to transcriptome studies, genes associated with adipocyte metabolism, adipokine secretion and cell signaling display a different pattern of expression between sWAT and vWAT [ 40 ], while pathway analysis has shown that genes implicated in inflammation are better expressed in vWAT than sWAT. The reason for these differences has not been fully elucidated but could be partly attributed to the passage of visceral fat products through the portal vein and the resultant drainage into the liver circulation, ultimately leading to systemic metabolic disease and low-grade inflammation [ 36 ].…”

Section: Adipose Tissue Physiologymentioning

confidence: 99%

The Potential Role of Exosomes in Child and Adolescent Obesity

et al. 2021

View full text Add to dashboard Cite

Child and adolescent obesity constitute one of the greatest contemporary public health menaces. The enduring disproportion between calorie intake and energy consumption, determined by a complex interaction of genetic, epigenetic, and environmental factors, finally leads to the development of overweight and obesity. Child and adolescent overweight/obesity promotes smoldering systemic inflammation (“para-inflammation”) and increases the likelihood of later metabolic and cardiovascular complications, including metabolic syndrome and its components, which progressively deteriorate during adulthood. Exosomes are endosome-derived extracellular vesicles that are secreted by a variety of cells, are naturally taken-up by target cells, and may be involved in many physiological and pathological processes. Over the last decade, intensive research has been conducted regarding the special role of exosomes and the non-coding (nc) RNAs they contain (primarily micro (mi) RNAs, long (l) non-coding RNAs, messenger (m) RNAs and other molecules) in inter-cellular communications. Through their action as communication mediators, exosomes may contribute to the pathogenesis of obesity and associated disorders. There is increasing evidence that exosomal miRNAs and lncRNAs are involved in pivotal processes of adipocyte biology and that, possibly, play important roles in gene regulation linked to human obesity. This review aims to improve our understanding of the roles of exosomes and their cargo in the development of obesity and related metabolic and inflammatory disorders. We examined their potential roles in adipose tissue physiology and reviewed the scarce data regarding the altered patterns of circulating miRNAs and lncRNAs observed in obese children and adolescents, compared them to the equivalent, more abundant existing findings of adult studies, and speculated on their proposed mechanisms of action. Exosomal miRNAs and lncRNAs could be applied as cardiometabolic risk biomarkers, useful in the early diagnosis and prevention of obesity. Furthermore, the targeting of crucial circulating exosomal cargo to tissues involved in the pathogenesis and maintenance of obesity could provide a novel therapeutic approach to this devastating and management-resistant pandemic.

show abstract

Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes

Cited by 26 publications

References 52 publications

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points

The Potential Role of Exosomes in Child and Adolescent Obesity

Contact Info

Product

Resources

About