Stearoyl‐CoA desaturase affects the level of global DNA methylation in 3T3‐L1 adipocytes

Abstract

Epigenetic modifications, including DNA methylation, play a central role in the regulation of lipid‐mediated metabolic pathways and energy metabolism. The aim of the present study was to elucidate whether stearoyl‐CoA desaturase 1 (SCD1), an important control point in lipid metabolism and body weight regulation, affects DNA methylation in adipocytes. Our study showed that the level of global DNA methylation is significantly reduced in 3T3‐L1 cells overexpressing SCD1. In contrast, both the silencing of SCD1 gene expression by siRNA and the treatment of cells with specific SCD1 inhibitor resulted in hipermethylation of DNA in 3T3‐L1 adipocytes. The changes in the level of DNA methylation correlated with the activity and expression level of methyltransferase 3a (DNMT3a). Interestingly, DNMT1 and DNMT3B were not affected by SCD1 expression. The effect of SCD1 on global DNA methylation was most pronounced in fully differentiated adipocytes. While the expression of adipogenic genes (C/EBPβ, C/EBPδ and PPARγ) was significantly increased in 3T3‐L1 cells overexpressing SCD1, the promoter methylation profiles of these genes did not differ between groups. Obtained results show that SCD1 regulates the level of DNA methylation in adipocytes and suggest that the mechanism by which SCD1 increases adipogenesis do not involve changes in methylation of the target gene promoters. Support: FNP TEAM/2010–5/2