OBJECTIVETo investigate the effect of niacin on HDL-induced cholesterol efflux and LXRalpha expression in adipocytes from hypercholesterolemic rabbits.

METHODSTwelve rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high cholesterol group (n = 6): maintained high cholesterol diet for 6 weeks; (2) niacin group (n = 6): the same cholesterol diet plus niacin (0.2 g . kg(-1). d(-1)) for 6 weeks. Control group (n = 6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for adipocyte culture. RT-PCR was used to evaluate adipocytes LXRalpha mRNA expressions. Cholesterol efflux rate was determined through measuring release of radioactivity from 3H-cholesterol prelabeled cells into medium containing HDL. The direct effect of niacin on LXRalpha and PPARgamma mRNA expression in primary rabbit adipocytes was assayed.

RESULTSHigh cholesterol diet resulted in decreased LXRalpha mRNA expressions and reduced cholesterol efflux rate in adipocytes. Six weeks of niacin treatment significantly enhanced the cholesterol efflux from adipocytes, which was related to the increased mRNA expressions of LXRalpha (r = 0.71, P < 0.05). In vitro study, niacin dose-dependently stimulated LXRalpha and PPARgamma mRNA expression in cultured adipocytes and there were positive correlations between various doses of niacin-induced cholesterol efflux and LXRalpha and PPARgamma mRNA expression (r = 0.83 P < 0.01, r = 0.76 P < 0.05, respectively).

CONCLUSIONLXRalpha and PPARgamma might play an important role in cholesterol efflux from adipocytes. Niacin can up-regulate LXRalpha and PPARgamma mRNA expressions and promote the cholesterol efflux in adipocytes from hypercholesterolemic rabbits.