Resistin induces lipolysis and re-esterification of triacylglycerol stores, and increases cholesteryl ester deposition, in human macrophages.
Human resistin, found within atheroma, exerts inflammatory, angiogenic and proliferative effects in vascular cells and may predict coronary events. Here, we investigate mechanisms by which resistin contributes to macrophage 'foam cell' formation. Increases in macrophage (THP-1) cholesteryl ester mass, in the presence or absence of oxidized LDL, were not explained by altered cholesterol efflux. Instead, resistin enhanced fractional turnover of the endogenous triacylglycerol pool, increased uptake and decreased oxidation of exogenous fatty acids, and decreased phosphorylation of acetyl CoA carboxylase, all factors increasing the availability of fatty acyl CoA substrate for acyl CoA: cholesterol acyltransferase-1, thereby enhancing macrophage cholesteryl ester deposition.
Rae
Colin
C
Vascular Biology Group, Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, United Kingdom.
Robertson
Stephanie A
SA
Taylor
Janice M W
JM
Graham
Annette
A
D000818:Animals; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D004951:Esterification; D006801:Humans; D008066:Lipolysis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D052243:Resistin / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D052243:Resistin; D014280:Triglycerides; C099252:oxidized low density lipoprotein