Fatty Acid Induced Hypermethylation in the <i>Slc2a4</i> Gene in Visceral Adipose Tissue Is Associated to Insulin-Resistance and Obesity

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 methylation of Slc2a4 persistently increases with the onset of obesity and insulin resistance, while gene expression progressively decreases. The regulatory impact of DNA methylation in the investigated enhancer region on SLC2A4 gene expression was validated with a reporter gene assay. Additionally, treatment of 3T3 pre-adipocytes with palmitate/oleate during differentiation decreased DNA methylation and increased Slc2a4 expression. These findings highlight a potential regulation of Slc2a4 by DNA methylation in VAT, which is induced by fatty acids and may play a role in the progression of obesity and insulin resistance in humans

Beobachtungspraktikum WS 16/17

Collegiate project conducted by the student research assistants of the chair of personality psychology at Humboldt-Universität zu Berlin. We aim to examine charitable behaviour as a form of prosocial behaviour in response to request by male vs. female recipients and for an ingroup as well as an outgroup condition. A concusional report will follow in due time. (Studentisches Projekt vom Lehrstuhl für Persönlichkeitspsychologie des Institutes für Psychologie der Humboldt-Universität zu Berlin. Wir untersuchen prosoziales Verhalten in Form von Spendenbereitschaft in Abhängigkeit von Effekten des Geschlechts der empfangenden Person und In- bzw. Out-Group. Ein abschließender Bericht folgt.