RMR-Related Expression Suppresses Adipogenesis in 3T3-L1 Cells.

Obesity causes various complications such as type 2 diabetes, hypertension, fatty liver, cardiovascular diseases, and cancer. In a pilot GWAS study, we screened the gene which is significantly related to the resting metabolic rate (RMR) in childhood obesity. With -overexpressed 3T3-L1 cells (Tg), we investigated the new obesity mechanism caused by an energy imbalance. After differentiation, lipid droplets (Oil red O staining) were not formed in Tg cells compared to the control. Tg preadipocyte fibroblast morphology was also not clearly observed in the cell morphology assay (DAPI/BODIPY). In Tg cells, the expression of PPARγ, C/EBPα, and aP2 (adipogenesis-related biomarkers) decreased 3-, 39-, and 200-fold, respectively. The expression of the adipokines leptin and adiponectin from adipose tissues also decreased 2.4- and 840-fold, respectively. In addition, the levels of pHSL(Ser563) and free glycerol, which are involved in lipolysis, were significantly lower in Tg cells than in the control. The reduction in insulin receptor expression in Tg cells suppressed insulin signaling systems such as AKT phosphorylation, and GLUT4 expression. Degradation of IRS-1 in 3T3-L1 adipocytes was caused by chronic exposure to insulin, but not Tg. Mitochondrial functions such as oxygen consumption and ATP production, as well as proton leak and UCP1 protein expression, decreased in Tg cells compared to the control. Moreover, autophagy was observed by increasing autophagosomal proteins, LC3, on Day 8 of differentiation in Tg cells. Through our first report on the gene related to RMR we found a new mechanism related to energy metabolism in obesity. expression positively suppressed adipogenesis, leading to the subsequent resistance of lipolysis, adipokine expression, insulin signaling, and mitochondrial functions.