Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats
Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats
复制标题
小檗碱降低MTTP启动子甲基化，减轻高脂饮食诱导的大鼠脂肪肝
DOI：
10.1194/jlr.m001958
复制
发表时间：
2010-09-01
影响因子：
6.5
通讯作者：
Gao, Xin
中科院分区：
文献类型：
--
作者：
Chang, XinXia;Yan, HongMei;Gao, Xin
High-calorie food leads to nonalcoholic fatty liver disease (NAFLD) through dysregulation of genes involved in lipid metabolism, but the precise mechanism remains unclear. DNA methylation represents one of the mechanisms that contributes to dysregulation of gene expression via interaction with environmental factors. Berberine can alleviate fatty liver in db/db and ob/ob mice. Here, we investigated whether DNA methylation is involved in the pathogenesis of NAFLD induced by a high-fat diet (HFD) and whether berberine improves NAFLD through influencing the methylation status of promoters of key genes. HFD markedly decreased the mRNA levels encoding CPT-1 alpha, MTTP, and LDLR in the liver. In parallel, DNA methylation levels in the MTTP promoter of rats with NAFLD were elevated in the liver. Interestingly, berberine reversed the downregulated expression of these genes and selectively inhibited HFD-induced increase in the methylation of MTTP. Consistently, berberine increased hepatic triglyceride (TG) export and ameliorated HFD-induced fatty liver. Furthermore, a close negative correlation was observed between the MTTP expression and its DNA methylation (at sites -113 and -20). These data indicate that DNA methylation of the MTTP promoter likely contributes to its downregulation during HFD-induced NAFLD and, further, that berberine can partially counteract the HFD-elicited dysregulation of MTTP by reversing the methylation state of its promoter, leading to reduced hepatic fat content.-Chang, X., H. Yan, J. Fei, M. Jiang, H. Zhu, D. Lu, and X. Gao. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J. Lipid Res. 2010. 51: 2504-2515.
