Effect of niacin on LXRalpha and PPARgamma expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits.
BACKGROUND
Adipose tissue contains a large amount of cholesterol and performs a buffer function for circulating cholesterol. Liver X receptors (LXR) alpha and peroxisome proliferator-activated receptor gamma (PPARgamma) might play a significant role in adipocyte cholesterol metabolism through mediation of cholesterol efflux. The aim of this study was to evaluate the effect of niacin on LXRalpha and PPARgamma expression and HDL-induced cholesterol efflux 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 (200 mg/kg/d) for 6 weeks. Control group (n=6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for adipocyte culture. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate adipocytes LXRalpha mRNA expressions. Cholesterol efflux rate was determined through measuring release of radioactivity from (3)H-cholesterol prelabeled cells into medium containing high-density lipoprotein (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 HDL-induced 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 in vitro study, niacin dose-dependently stimulated LXRalpha and PPARgamma mRNA expression in cultured adipocytes. And various doses of niacin-induced cholesterol efflux was positive correlation with LXRalpha and PPARgamma mRNA expression (r=0.83 P<0.01; r=0.76 P<0.05; respectively).


CONCLUSIONS
Niacin can up-regulate LXRalpha and PPARgamma mRNA expression and promote the HDL-induced cholesterol efflux in adipocytes from hypercholesterolemic rabbits.
Zhao
Shui-ping
SP
Department of Cardiology, The Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 86, Changsha, Hunan 410011, PR China. zhaosp@medmail.com.cn
Yang
Jun
J
Li
Jing
J
Dong
Shao-zhuang
SZ
Wu
Zhi-hong
ZH
D017667:Adipocytes / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia / Q000188:drug therapy; D000071518:Liver X Receptors; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D012333:RNA, Messenger / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D009525:Niacin; D002784:Cholesterol