Hormone and pharmaceutical regulation of ASP production in 3T3-L1 adipocytes

• Published in: Journal of cellular biochemistry Vol. 109; no. 5; pp. 896 - 905
• Main Authors: Gao, Ying, Gauvreau, Danny, Cianflone, Katherine
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2010
• Subjects: 3T3-L1 Cells; adipocyte; Adipocytes - drug effects; Adipocytes - metabolism; adipokine secretion; Adrenergic beta-Antagonists - pharmacology; Animals; Chylomicrons - metabolism; Complement C3 - biosynthesis; fatty acid uptake; Fatty Acids, Nonesterified - metabolism; Hormones - pharmacology; Intercellular Signaling Peptides and Proteins - biosynthesis; Mice; Pharmaceutical Preparations - metabolism; Triglycerides - metabolism
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.22464

Several studies have demonstrated increases in acylation stimulating protein (ASP), and precursor protein C3 in obesity, diabetes and dyslipidemia, however the nature of the regulation is unknown. To evaluate chronic hormonal and pharmaceutical mediated changes in ASP and potential mechanisms, 3T3‐L1 adipocytes were treated with physiological concentrations of relevant hormones and drugs currently used in treatment of metabolic diseases for 48 h. Medium ASP production and C3 secretion were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride (TG) mass, non‐esterified fatty acid (NEFA) release and real‐time FA uptake). Chylomicrons increased ASP production (up to 411 ± 133% P < 0.05), while leptin, triiodothyronine, and β‐blockers atenolol and propranolol had no effect. Dexamethasone, lovastatin, rosiglitazone and rimonabant decreased ASP production (−53 to −85%, P < 0.05), associated with a decrease in the precursor protein C3 (−37% to −65%, P < 0.01). By contrast, epinephrine, progesterone, testosterone, angiotensin II and metformin also decreased ASP (−54% to −100%, P < 0.05), but without change in precursor protein C3, suggesting a direct effect on convertase activity, possibly mediated by interference (except metformin) due to marked increases in NEFA (5.6–31‐fold, increased P < 0.05). Both lovastatin and metformin induced decreases in ASP were also associated with decreased TG mass (maximal −60%, P < 0.05) and real‐time FA uptake (maximum −75%, P < 0.05), suggesting a change in adipocyte differentiation status. These in vitro results are consistent with in vivo ASP profiles in subjects, and suggest that ASP may be regulated through precursor C3 availability, convertase activity and differentiation status. J. Cell. Biochem. 109: 896–905, 2010. © 2010 Wiley‐Liss, Inc.