Reduction of Lipid Accumulation in HepG2 Cells by Luteolin is associated with Activation of AMPK and Mitigation of Oxidative Stress

被引：138

作者：

Liu, Jin-Feng ^{[1
]}

Ma, Ying ^{[1
]}

Wang, Ying ^{[1
]}

Du, Zhi-Yan ^{[1
]}

Shen, Jing-Kang ^{[1
]}

Peng, Hong-Li ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

来源：

PHYTOTHERAPY RESEARCH | 2011年 / 25卷 / 04期

基金：

中国国家自然科学基金;

关键词：

luteolin; AMPK; SREBP-1c; FAS; CPT-1; reactive oxygen species; PROTEIN-KINASE; INSULIN-RESISTANCE; OBESITY; CANCER; ROSIGLITAZONE; INDUCTION; MECHANISM; PREVENTS; DISEASE; RAT;

D O I：

10.1002/ptr.3305

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The present study was carried out to investigate the lipid-lowering effect of luteolin by using a cell model of steatosis induced by palmitate. Incubation of HepG2 cells with palmitate markedly increased lipid accumulation (Oil Red O staining), the genes involved in lipogenesis, including fatty acid synthase (FAS) and its upstream regulator sterol regulatory element binding protein 1c (SREBP-1c), and reactive oxygen species (ROS) production. Luteolin enhanced the phosphorylation of AMP-activated protein kinase alpha (AMPK alpha) and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated gene expression of carnitine palmitoyl transferase 1 (CPT-1), which is the rate-limiting enzyme in mitochondrial fatty acid beta-oxidation, and down-regulated SREBP-1c and FAS mRNA levels in the absence and presence of palmitate. In addition, luteolin significantly decreased ROS production and ameliorated lipid accumulation in HepG2 cells caused by palmitate. Furthermore, intracellular triglyceride (TG) measurement indicated that the luteolin-mediated reduction of enhanced TG caused by palmitate was blocked by pretreatment with the AMPK inhibitor, compound C. The results suggested that the lipid-lowering effect of luteolin might be partially mediated by the up-regulation of CPT-1 and down-regulation of SREBP-1c and FAS gene expression, possibly by activation of the AMPK signaling pathway, and partially might be through its antioxidative actions. Copyright (C) 2010 John Wiley & Sons, Ltd.

引用

页码：588 / 596

页数：9

共 35 条

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