Palmitate and oleate induction of acylation stimulating protein resistance in 3T3-L1 adipocytes and preadipocytes.
Acylation stimulating protein (ASP) stimulates triglyceride synthesis and glucose transport via its receptor C5L2. The aims were (i) to evaluate ASP response under insulin-resistant conditions and (ii) to identify mechanisms of ASP resistance using 3T3-L1 adipocytes and preadipocytes. Overnight incubation with palmitate (PAL) or oleate (OLE) induced dose-dependent inhibition of ASP-stimulated glucose transport in adipocytes (198 +/- 18% +ASP, 100 +/- 4% basal, 131 +/- 14% + ASP + 1 mmol/L PAL) and preadipocytes (287 +/- 21% + ASP, 100 +/- 4% basal, 109 +/- 13% + ASP + 1 mmol/L PAL). In adipocytes, dose-dependent maximal C5L2 mRNA decreases were -41 +/- 15% and -82 +/- 2%, with decreased cell-surface C5L2 of -55 +/- 12% and -39 +/- 9% (1 mmol/L PAL and OLE, respectively) with no change in preadipocytes. Adipocytes treated with PAL or OLE evidenced inhibition of ASP stimulation of G proteins: Gbeta (-50%), Galphaq/11 (-50%) and protein kinase C: PKCalpha-P (-52%), PKCzeta-P (-43%). Fatty acid-induced ASP resistance via C5L2 may contribute to altered adipose tissue function and obesity/insulin resistance phenotype in humans.
Wen
Yu
Y
Department of Pediatrics, Tongji Hospital, HuaZhong University of Science and Technology, Wuhan, Hubei, PR China.
Wang
HongWei
H
MacLaren
Robin
R
Wu
Jing
J
Lu
HuiLing
H
Cianflone
Katherine
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D003176:Complement C3 / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology*; D010168:Palmitates / Q000494:pharmacology*; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine / Q000378:metabolism*
C000594938:C5ar2 protein, mouse; D003176:Complement C3; D010168:Palmitates; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D019301:Oleic Acid; D019204:GTP-Binding Proteins