Abstract 18952: Mir-130 Targets Apcdd1 Expression to Inhibit Adipocyte Differentiation: Role in Diet-Induced Obesity

Background: Impaired adipocyte differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to cardiometabolic disease. We recently reported that adenomatosis polyposis coli downregulated 1 (APCDD1) stimulates adipocyte differentiation by repressing Wnt signaling. Here, we examined the impact of high fat diet (HFD) on adipocyte differentiation and APCDD1 expression and uncovered a novel epigenetic regulatory mechanism involving miR-130 that may contribute to the pathogenesis of DIO. Methods and Results: APCDD1 expression was significantly upregulated in mature adipocytes as compared to undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues. siRNA-based silencing of APCDD1 in preadipocytes markedly increased Wnt signaling (Wnt, LRP5, β-catenin) and inhibited adipocyte gene (C/EBPα, PPARγ) expression and lipid droplet accumulation, while adenoviral-mediated overexpression of APCDD1 enhanced adipocyte differentiation. Not...