Abstract 14689: SDPR/Cavin-2 Regulates Adipocyte Differentiation With Suppression of PPAR? and C/EBP? Expressions in 3T3L1 Cells

Introduction:Congenital generalized lipodystrophy is an autosomal recessive disorder characterized by deficiency of adipose tissue which is evident at birth and is accompanied by a severe resistance to insulin, leading to hyperglycemia. The plasma membrane of adipocytes is endowed with abundant caveolae, involved in insulin signaling and lipid homeostasis. Mutation of caveolar-related proteins, such as Caveolin-1, Caveolin-3 and Cavin-1, are known to cause lipodystrophies in humans. SDPR/Cavin-2, one of the caveolar-related proteins, is also highly expressed in adipocytes. However, the association between SDPR/Cavin-2 and adipocyte differentiation is not well known.Objective:To clarify the relationship between SDPR/Cavin-2 and adipocyte differentiation.Methods and Results:We first measured SDPR/Cavin-2 expression level in 3T3L1 pre-adipocyte cells under adipocyte differentiation. SDPR/Cavin-2 mRNA expression was increased more than 10-fold elevation during differentiation. Next, we evaluated lipid accumulation after adipocyte differentiation in 3T3L1 cells using by BODIPY (boron-dipyrromethene) lipid probe stains. FACS analysis showed lipid accumulation in 3T3L1 cells was significantly decreased by SDPR/Cavin-2 knockdown using siRNAs. Adipocyte differentiation requires the transcriptional activity of peroxisome proliferator-activated receptor-? (Ppar?) and CCAAT/enhancer binding proteins (C/Ebp?). Ppar? and C/Ebp?mRNA expressions in 3T3L1 cells under differentiationwere markedly decreased by SDPR/Cavin-2 knockdown. Adipocytes play a central role in maintaining metabolic homeostasis, especially glucose-insulin signaling. In vivostudy, SDPR/Cavin-2 knockout (KO) mice exhibited a higher blood glucose level in an intraperitoneal glucose tolerance test compared with wild-type mice, suggesting SDPR/Cavin-2 KO mice have insulin resistance.Conclusions:Our findings suggest that SDPR/Cavin-2 promotes adipocyte differentiation via PPAR? and C/EBP? Expression. SDPR/Cavin-2 may affect metabolic homeostasis through adipocyte differentiation.