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  • Title: Niacin promotes cholesterol efflux through stimulation of the PPARgamma-LXRalpha-ABCA1 pathway in 3T3-L1 adipocytes.
    Author: Wu ZH, Zhao SP.
    Journal: Pharmacology; 2009; 84(5):282-7. PubMed ID: 19797938.
    Abstract:
    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.
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