title: 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 micromol/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 adipocytes, p < 0.05). Conversely, 1 micromol/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.
authors.affiliation: Medicine, McGill University Health Center, Montreal, Canada.
authors.forename: R
authors.initials: R
authors.lastname: MacLaren
authors.forename: D
authors.initials: D
authors.lastname: Kalant
authors.forename: K
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000215:Acylation; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D015926:Complement C3a / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C000594938:C5ar2 protein, mouse; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C044541:complement C3a, des-Arg-(77)-; D003907:Dexamethasone; D015926:Complement C3a; C089946:2,4-thiazolidinedione