Niacin promotes cholesterol efflux through stimulation of the PPARgamma-LXRalpha-ABCA1 pathway in 3T3-L1 adipocytes.
BACKGROUND
The mechanism by which niacin increases plasma levels of high-density lipoprotein cholesterol (HDL-C) is not clearly understood yet. Adipocytes contain the largest pool of free cholesterol in the body and might play a significant role in cholesterol metabolism. Despite preferential accumulation in adipose tissue, it is not clear whether the actions of niacin on cholesterol efflux from adipocytes contribute to its HDL-raising effect.


METHODS
Fully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentrations of niacin (0-1.0 mmol/l) for 24 h. Reverse transcription polymerase chain reaction was used to evaluate peroxisome proliferator-activated receptor-gamma (PPARgamma), LXRalpha and ABCA1 mRNA expression in adipocytes. Cholesterol efflux rate was determined by measuring the release of radioactivity from (3)H-cholesterolprelabeled cells into medium containing apolipoprotein A-I (ApoA-I).


RESULTS
Niacin dose-dependently stimulated PPARgamma, LXRalpha and ABCA1 mRNA expression and promoted ApoA-I-induced cholesterol efflux in adipocytes. Treatment of PPARgamma-selective antagonist GW9662 significantly abolished the niacin-induced increase in LXRalpha and ABCA1 mRNA expression and cholesterol efflux to ApoA-I.


CONCLUSIONS
Niacin may promote cholesterol efflux from adipocytes to ApoA-I via activation of the PPARgamma-LXRalpha-ABCA1 pathway. To some extent, this effect might help to explain the possible mechanism by which niacin increases plasma HDL-C levels.
Wu
Zhi-Hong
ZH
Department of Cardiology, Second Xiangya Hospital, Central South University, Hunan 410011, PR China.
Zhao
Shui-Ping
SP
D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D000071518:Liver X Receptors; D051379:Mice; D009525:Niacin / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D009525:Niacin