Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats
Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats
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DOI：
10.1002/mnfr.201200237
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发表时间：
2012-11-01
影响因子：
5.2
通讯作者：
Arola-Arnal, Anna
中科院分区：
文献类型：
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作者：
Baselga-Escudero, Laura;Blade, Cinta;Arola-Arnal, Anna
范围 西方国家的一个主要健康问题是脂肪酸和胆固醇代谢失调，导致代谢综合征等病症。我们小组之前的研究表明，原花青素是人类饮食中最丰富的多酚，可调节脂质代谢，是有效的降血脂剂。非编码 RNA miR-33 和 miR-122 调节参与脂质代谢的基因。方法和结果在这里，我们发现葡萄籽原花青素在体内和体外快速且短暂地抑制大鼠肝细胞中 miR-33 和 miR-122 的表达。此外，miR-33靶基因ATP结合盒A1和miR-122靶基因脂肪酸合酶也受到原花青素的调节。具体来说，改变 miRNA 水平后，ATP 结合盒 A1 mRNA 和蛋白质水平增加，脂肪酸合酶 mRNA 和蛋白质水平降低。结论 这些结果表明，原花青素治疗通过抑制 miR-33 增加肝脏胆固醇流出以产生新的 HDL 颗粒，并通过抑制 miR-122 减少脂肪生成。这些结果强调了葡萄籽原花青素通过影响脂质代谢的 miRNA 调节剂而产生低脂血症的新机制。
Scope One major health problem in westernized countries is dysregulated fatty acid and cholesterol metabolism that causes pathologies such as metabolic syndrome. Previous studies from our group have shown that proanthocyanidins, which are the most abundant polyphenols in the human diet, regulate lipid metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and miR-122, regulate genes that are involved in lipid metabolism. Methods and results Here, we show that grape seed proanthocyanidins rapidly and transiently repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR-122 target gene fatty acid synthase were also modulated by proanthocyanidins. Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and fatty acid synthase mRNA and protein levels were reduced after the miRNA levels were altered. Conclusion These results suggest that proanthocyanidin treatment increased hepatic cholesterol efflux to produce new HDL particles by repressing miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight a new mechanism by which grape seed proanthocyanidins produce hypolipidemia through their effects on miRNA modulators of lipid metabolism.