Sex steroid hormones induce acylation stimulating protein resistance in 3T3-L1 adipocytes

✍ Scribed by Yu Wen; HongWei Wang; Robin MacLaren; HuiLing Lu; Xiu-Fen Hu; Katherine Cianflone

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 400 KB
• Volume: 105
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21838

✦ Synopsis

Abstract

Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. In human studies, ASP is increased in insulin resistant states such as obesity, diabetes, polycystic ovary syndrome and late pregnancy (the latter two associated with altered sex hormones). The aims were (i) to evaluate ASP response and C5L2 expression following treatment with sex steroid hormones and (ii) to identify mechanisms of ASP resistance using 3T3‐L1 adipocytes and preadipocytes. Overnight incubation with physiological progesterone (PROG) concentrations induced dose‐dependent inhibition of ASP‐stimulated glucose transport in adipocytes (188 ± 11% +ASP, 100 ± 4% control, 129 ± 18% to 85 ± 7% [ASP + PROG 10^−8^ to 10^−6^ M] and preadipocytes (263 ± 18% +ASP, 100 ± 3% control, 170 ± 11% to 167 ± 4% [ASP + PROG 10^−8^ to 10^−6^ M]), while estradiol and testosterone (TEST) were effective only at the highest concentration (10^−6^ M). In adipocytes, dose‐dependent maximal C5L2 mRNA decreases were 39–75% (P = 0.003), with decreased cell‐surface C5L2 of −22% and −27% (10^−6^ M PROG and TEST, respectively) with no change in preadipocytes. Adipocytes treated with PROG displayed decreases in G proteins: Gβ (−55%), Gαq/11 (−56%) as well as complete inhibition of ASP stimulation. PROG significantly decreased basal levels of phosphorylated PKCα (p‐PKCα) while there was no change in p‐ PKCζ. ASP increased p‐PKCα and PKCζ to 161% (P < 0.0.001) and 160% (P < 0.01), a stimulation effectively blocked by PROG (10^−8^ and 10^−6^ M) and TEST (10^−6^ M). Sex steroid hormone‐induced ASP resistance via C5L2 may contribute to altered adipose tissue function and insulin resistance phenotype in humans. J. Cell. Biochem. 105: 404–413, 2008. © 2008 Wiley‐Liss, Inc.