[Effect of niacin on HDL-induced cholesterol efflux and LXRalpha expression in adipocytes of hypercholesterolemic rabbits].
OBJECTIVE
To investigate the effect of niacin on HDL-induced cholesterol efflux and LXRalpha expression in adipocytes from hypercholesterolemic rabbits.


METHODS
Twelve 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.


RESULTS
High 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).


CONCLUSIONS
LXRalpha 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.
Yang
Jun
J
Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha 410011, China.
Zhao
Shui-ping
SP
Li
Jing
J
Wu
Zhi-hong
ZH
Dong
Shao-zhuang
SZ
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D009525:Niacin / Q000494:pharmacology* / Q000627:therapeutic use; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000378:metabolism; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; D009525:Niacin; D002784:Cholesterol