(2013) Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases, Epigenetics, 8:9,[935][936][937][938][939][940][941][942][943]

BackgroundLeptin (LEP) and adiponectin (ADIPOQ) genes encode adipokines that are mainly secreted by adipose tissues, involved in energy balance and suspected to play a role in the pathways linking adiposity to impaired glucose and insulin homeostasis. We have thus hypothesized that LEP and ADIPOQ DNA methylation changes might be involved in obesity development and its related complications. The objective of this study was to assess whether LEP and ADIPOQ DNA methylation levels measured in subcutaneous (SAT) and visceral adipose tissues (VAT) are associated with anthropometric measures and metabolic profile in severely obese men and women. These analyses were repeated with DNA methylation profiles from blood cells obtained from the same individuals to determine whether they showed similarities.MethodsPaired SAT, VAT and blood samples were obtained from 73 severely obese patients undergoing a bioliopancreatic diversion with duodenal switch. LEP and ADIPOQ DNA methylation and mRNA levels were quantified using bisulfite-pyrosequencing and qRT-PCR respectively. Pearson’s correlation coefficients were computed to determine the associations between LEP and ADIPOQ DNA methylation levels, anthropometric measures and metabolic profile.ResultsDNA methylation levels at the ADIPOQ gene locus in SAT was positively associated with BMI and waist girth whereas LEP DNA methylation levels in blood cells were negatively associated with body mass index (BMI). Fasting LDL-C levels were found to be positively correlated with DNA methylation levels at LEP-CpG11 and -CpG17 in blood and SAT and with ADIPOQ DNA methylation levels in SAT (CpGE1 and CpGE3) and VAT (CpGE1).ConclusionsThese results confirm that LEP and ADIPOQ epigenetic profiles are associated with obesity. We also report associations between LDL-C levels and both LEP and ADIPOQ DNA methylation levels suggesting that LDL-C might regulate their epigenetic profiles in adipose tissues. Furthermore, similar correlations were observed between LDL-C and LEP blood DNA methylation levels suggesting a common regulatory pathway of DNA methylation in both adipose tissues and blood.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0174-1) contains supplementary material, which is available to authorized users.

Background: An excess of adipose tissue mass is generally featured by local patches of hypoxia and increased concentrations of persistent organic pollutants (POPs) at the adipose tissue level. These two features have independently been reported to trigger inflammatory responses within adipocytes. Objective and Methods: In this study, we determined the combined effect of hypoxia and exposure to a prevalent coplanar polychlorinated biphenyl, PCB-77, on adiponectin (anti-inflammatory) and interleukin-6 (IL-6, pro-inflammatory) secretion from differentiated human preadipocytes. Upon differentiation, adipocytes were exposed to PCB-77 (3.4mM and 340mM) and incubated under various oxygen levels (21%, 8%, and 2%) for 24hrs. Following the exposure period, culture media was recuperated and adipokine levels were quantified by ELISA. Results: Adiponectin secretion was significantly decreased when adipocytes were exposed to 3.4mM and 340mM PCB-77, as well as at 2% O 2 . Adiponectin secretion decreased in parallel with the levels of PCB-77 at 8% O 2 while there was no additional effect of PCB-77 at 2% O 2 . Regarding IL-6, there was a concentration dependent increase as O 2 fell. However, IL-6 secretion significantly decreased following exposure to high level of PCB-77. IL-6 secretion decreased in parallel with the levels of PCB-77 and this, regardless of O 2 level. Conclusion: These findings support the hypothesis that local adipose tissue hypoxia and an accumulation of POPs both contribute to chronic, low-grade inflammation often observed during obesity.

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