Niacin can reduce leptin in a rabit model of hypercholesterolemia.

Abstract

BACKGROUND: Leptin may play an important role in the development of atherosclerosis. Several transcription genes [including peroxisome proliferator-activated receptor gamma (PPARgamma) and CD36] involved in lipid and glucose metabolism and inflammatory processes may correlate to leptin expression. The aim of this study was to investigate the effect of niacin on serum leptin levels in hypercholesterolemic rabbits and the expression of leptin, PPARgamma, and CD36 in adipocytes from hypercholesterolemic rabbits. METHODS: Eighteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (a) high-cholesterol group (n=6), which is maintained on high-cholesterol diet for 6 weeks, and (b) niacin group (n=6), which receives the same cholesterol diet plus niacin (200 mg/kg/day) for 6 weeks. The control group (n=6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of niacin on leptin release was assayed in hypercholesterolemic rabbit adipocytes. Leptin levels in serum and adipocyte culture supernatant were measured via enzyme-linked immunosorbent assay. RT-PCR was used to evaluate leptin, PPARgamma, and CD36 mRNA expression in adipose and adipocytes. RESULTS: Compared with the control group, rabbits fed with high-cholesterol diets showed higher levels of serum total cholesterol, low-density lipoprotein cholesterol, and leptin, all of which were significantly reduced by niacin treatment. After 6 weeks of treatment with niacin, the leptin level was significantly decreased by 21.8% (6.87+/-1.58 vs. 8.79+/-1.45, P<.05) and leptin mRNA expression of adipose was significantly lower in rabbits treated with niacin than in those fed with high-cholesterol diet continuously (0.58+/-0.11 vs. 0.73+/-0.15, P<.05). Niacin dose-dependently inhibited leptin secretion and increased CD36 and PPARgamma expression in cultured adipocytes. The reduction of leptin mRNA expression of hypercholesterolemic rabbits by niacin was negatively correlated with the up-regulation of PPARgamma and CD36 mRNA expression by niacin (r=-.69 and r=-.63, respectively, P<.01). CONCLUSION: Niacin can reduce serum level and adipose mRNA expression of leptin and up-regulate PPARgamma and CD36 mRNA expression in hypercholesterolemic rabbits.