Fatty Acid Induced Hypermethylation in the Slc2a4 Gene in Visceral Adipose Tissue Is Associated to Insulin-Resistance and Obesity.

ABSTRACT: De novo lipogenesis (DNL) in visceral adipose tissue (VAT) is associated with systemic insulin sensitivity. DNL in VAT is regulated through ChREBP activity and glucose uptake through Glut4 (encoded by Slc2a4). Slc2a4 expression, ChREBP activity, and DNL are decreased in obesity, the underlying cause however remains unidentified. We hypothesize that increased DNA methylation in an enhancer region of Slc2a4 decreases Slc2a4 expression in obesity and insulin resistance. We found that SLC2A4 expression in VAT of morbidly obese subjects with high HbA1c (>6.5%, n = 35) is decreased, whereas DNA methylation is concomitantly increased compared to morbidly obese subjects with low HbA1c (≤6.5%, n = 65). In diet-induced obese (DIO) mice, DNA methylatio

SUBMITTER: Britsemmer JH 

PROVIDER: S-EPMC10094548 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature