Regional distribution of body fat in relation to DNA methylation within the LPL, ADIPOQ and PPARγ promoters in subcutaneous adipose tissue

Abstract

Obesity may be related to differential DNA methylation and thus to differential expression of key genes in adipose tissue metabolism, such as LPL, ADIPOQ and PPARγ. Using subcutaneous adipose tissue (SAT) from 59 individuals of the European Prospective Investigation into Cancer and Nutrition–Potsdam study, we performed quantitative DNA methylation analysis within the promoters of LPL (LPL-CG1 and -CG2), ADIPOQ (ADIPOQ-CG1 and-CG2) and PPARγ (PPARγ-CG1). We then studied DNA methylation in relation to SAT gene expression, body composition measured using whole-body magnetic resonance imaging, body mass index (BMI), waist circumference (WC) and long-term changes in BMI and WC. For LPL-CG1 and LPL-CG2, higher methylation levels were associated with lower LPL expression, but with higher past WC gain. LPL-CG1 was also positively associated with BMI, WC, and visceral and subcutaneous fat mass. ADIPOQ-CG1 or -CG2 methylation exhibited no association with ADIPOQ expression or with anthropometric parameters. PPARγ-CG1 methylation was significantly higher in individuals with higher visceral fat mass. Among the investigated sites, LPL-CG1 methylation showed the strongest association with gene expression and regional body fat distribution, thereby possibly linking the degree of obesity with major metabolic processes in SAT.

Obesity-induced insulin resistance via changes in the DNA methylation profile of insulin pathway genes

“…Summarizing all of the data described above (ours and others 19,[11][12][13][33][34][35] ), we suggest that IR is epigenetically regulated and thus potentially could be reversed. However, this statement has not been confirmed to date.…”

“…The relationship between DNA methylation and IR has been shown by other researchers, who described promoter methylation of other genes regulating IR, such as the adiponectin 19 , leptin and PPARγ genes, etc. [11][12][13] The potential mechanism regulating the methylation status of the adiponectin gene was related to increased expression of DNMT1, stimulated by TNF-α. 19 In our study, we have shown altered expression of DNMT3a in both types of tissues, as the potential reason for differently methylated global and sitespecific DNA methylation, especially insulin signaling pathway genes.…”

“…[6][7][8][9][10] Indeed, abundant data implicate obesity in DNA hypermethylation at both global and site-specific levels, including genes regulating insulin sensitivity, such as ADIPOQ, LPL, or PPARγ. [11][12][13] Zheng et al reported a link between obesity and methylation of mtDNA (mitochondrial DNA). 14 Analysis of DNA methylation carried out before and after weight loss revealed a differentially methylated region of the genome correlated with numerous genes, including 21 genes regulating insulin sensitivity.…”

‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue

“…Differential methylation of the gene ( LPL ) encoding lipoprotein lipase (which hydrolyses circulating triglyceride‐rich lipoproteins with subsequent fatty acid uptake into the adipose tissue) might be linked to obesity and regional fat distribution (Drogan et al . ). Finally, obesity‐induced inflammation induces a specific miRNA pattern in adipocytes and macrophages (Ortega et al .…”

LPL methylation of peripheral blood leukocytes - Prophet of atherothrombotic stroke

“…It had been proved that LPL gene methylation are associated with plasma lipid levels in patients with familial hypercholesterolemia (FH), which might be an underlying molecular mechanism obligated to dyslipidemia [21,22].Placental LPL methylation levels were associated with gestational diabetes and maternal blood lipids as well [23]. Ana Arpón et al also detected that LPL methylation in peripheral leukocytes was related to insulin sensitivity in non-diabetic young women [24] D Drogan et al reported that regional distribution of body fat was in relation to LPL methylation likewise [25]. Moreover, Daniel Castellano-Castillo discovered that adipose tissue LPL methylation was in association with triglyceride concentrations in the metabolic syndrome [26].…”