烟酸对3T3-L1脂肪细胞胆固醇流出的影响

Effect of Niacin on Cholesterol Efflux in 3T3-L1 Cells

目的观察烟酸对分化成熟的3T3-L1脂肪细胞胆固醇流出的影响,并探讨其机制。方法3T3-L1细胞促分化成熟后,给与不同浓度的烟酸(0～1.0mmol/L)干预24h后,收集细胞,逆转录聚合酶链反应测定脂肪细胞三磷酸腺苷结合盒转运体A1、B族Ⅰ型清道夫受体和过氧化体增殖物激活型受体γmRNA表达,采用液体闪烁计数器检测细胞内胆固醇流出。结果烟酸呈剂量依赖性增加脂肪细胞三磷酸腺苷结合盒转运体A1mRNA的表达,并促进载脂蛋白AⅠ介导的胆固醇流出,但对B族Ⅰ型清道夫受体表达无影响。过氧化体增殖物激活型受体γ在分化成熟的3T3-L1脂肪细胞有较高水平的表达,与空白组(0.38±0.29)比较,在1.0mmol/L浓度的烟酸干预时过氧化体增殖物激活型受体γ表达明显升高(3.15±0.96),为空白组的8.3倍。结论烟酸可通过上调过氧化体增殖物激活型受体γ表达,促进脂肪细胞载脂蛋白AⅠ—三磷酸腺苷结合盒转运体A1通路,加速细胞内胆固醇流出。这可能为解释烟酸升高高密度脂蛋白胆固醇的机制提供有用的线索。

Aim To explore the effect of niacin on cholesterol efllux in fully differentiated 3T3- L1 cells and the pessible mechanism. Methods Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentration of niacin （0 ～ 1.0 mmol/L） for 24 h （ n = 6）. Reverse transcription polymerase chain reaction （RT-PCR） was used to evaluate adipocytes mRNA expression. Cholesterol efllux rate was determined through measuring release of radioactivity from 3H-cholesterol prelabled cells into medium containing apolipoprotein A Ⅰ . Results Niacin could dose-dependendy increase adenosine triphosphate binding cassette transporter A1 （ ABCA1 ） mRNA expression and apolipoprotein A Ⅰ -mediated cholesterol efllux in 3T3-L1 cells, but had no effect on scavenger receptor class B type I mRNA expression. Peroxisome proliferator-activated receptor gamma （PPARγ） presented high level expression in fully differentiated 3T3-L1 cells. Compared with control （0.38 ± 0. 29）, niacin significantly enhanced PPARγ mRNA expression. The maximal induction was obtained with 1.0 mmol/L of niacin, Conclusion Niacin could enhance the ABCA1 pathway in adipocytes, up-regulate PPARγ mRNA expression, then increase cholesterol efllux. This new action of niacin might provide rational explaination to the mechanisms of miring high-density hpoprorein cholesterol.