The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance

Abstract

Acylation-stimulating protein (ASP) and interaction with its receptor C5L2 influences adipocyte metabolism. We examined insulin resistance and differentiation-mediated regulation of C5L2 and the mechanistic impact on both C5L2 cell-surface protein and ligand binding to the receptor. C5L2 mRNA increased 8.7-fold with differentiation in 3T3-L1 cells (p < 0.0001) by day 9. In preadipocytes, insulin and dexamethasone increased C5L2 mRNA (1 μmol/L insulin resulted in a 2.6-fold increase, p < 0.01; 10 nmol/L dexamethasone resulted in a 17.9-fold increase, p < 0.01) and C5L2 cell-surface protein (100 nmol insulin resulted in a 2.7-fold increase, p < 0.001; 10 nmol/L dexamethasone resulted in a 2.8-fold increase, p < 0.001). In adipocytes, 100 nmol/L insulin increased C5L2 mRNA and ASP binding (respectively, 1.3-fold, p < 0.01; and 2.4-fold, p < 0.05). Dexamethasone decreased ligand binding (–60%, p < 0.02) without changing mRNA. Tumor necrosis factor alpha decreased C5L2 mRNA (–88% in preadipocytes and –38% in adipocytes, p < 0.001), C5L2 cell-surface protein (–53% in preadipocytes, p < 0.0001), and ASP binding (–60% and –49% in, respectively, preadipocytes and adipoctyes, p < 0.05). Conversely, 1 μmol/L and 10 nmol/L rosiglitazone increased, respectively, C5L2 mRNA (9.3-fold, p < 0.0001) and ASP binding (2.4-fold, p < 0.05). Thus, C5L2 mRNA increases with differentiation, insulin, and thiazolidinedione treatment, and decreases with tumor necrosis factor alpha, all of which results in functional changes in ASP–C5L2 response and may have implications for human metabolism.