RMR-Related DNAJC6 Expression Suppresses Adipogenesis in 3T3-L1 Cells

Cells

Myoungsook Lee¹  Juhee Kim¹ 

[1] Department of Food & Nutrition, Sungshin Women’s University, Seoul 01133, Korea;

关键词: obesity;    DNAJC6;    insulin pathway;    inflammatory cytokines;    autophagy;    thermogenesis;   

DOI  :  10.3390/cells11081331

来源: DOAJ

【 摘 要 】

Obesity causes various complications such as type 2 diabetes, hypertension, fatty liver, cardiovascular diseases, and cancer. In a pilot GWAS study, we screened the DNAJC6 gene which is significantly related to the resting metabolic rate (RMR) in childhood obesity. With DNAJC6-overexpressed 3T3-L1 cells (Tg^Hsp), we investigated the new obesity mechanism caused by an energy imbalance. After differentiation, lipid droplets (Oil red O staining) were not formed in Tg^Hsp cells compared to the control. Tg^Hsp preadipocyte fibroblast morphology was also not clearly observed in the cell morphology assay (DAPI/BODIPY). In Tg^Hsp 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^Hsp cells than in the control. The reduction in insulin receptor expression in Tg^Hsp 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^Hsp. Mitochondrial functions such as oxygen consumption and ATP production, as well as proton leak and UCP1 protein expression, decreased in Tg^Hsp cells compared to the control. Moreover, autophagy was observed by increasing autophagosomal proteins, LC3, on Day 8 of differentiation in Tg^Hsp cells. Through our first report on the DNAJC6 gene related to RMR, we found a new mechanism related to energy metabolism in obesity. DNAJC6 expression positively suppressed adipogenesis, leading to the subsequent resistance of lipolysis, adipokine expression, insulin signaling, and mitochondrial functions.

【 授权许可】

Unknown