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学科主题: 基础医学
题名:
Suppression of 2,3-Oxidosqualene Cyclase by High Fat Diet Contributes to Liver X Receptor-alpha-mediated Improvement of Hepatic Lipid Profile
作者: Dang, Huaixin1; Liu, Yan1; Pang, Wei1; Li, Chenghong1; Wang, Nanping2; Shyy, John Y. -J.3; Zhu, Yi1
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2009-03-06
DOI: 10.1074/jbc.M803702200
卷: 284, 期:10, 页:6218-6226
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: VASCULAR ENDOTHELIAL-CELLS ; ELEMENT-BINDING PROTEIN-1C ; CHOLESTEROL HOMEOSTASIS ; TRANSCRIPTION FACTOR ; OXYSTEROL RECEPTORS ; LANOSTEROL CYCLASE ; ACID SYNTHESIS ; LXR-ALPHA ; LIGAND ; ATHEROSCLEROSIS
英文摘要:

The liver X receptors (LXRs) sense oxysterols and regulate genes involved in cholesterol metabolism. Synthetic agonists of LXRs are potent stimulators of fatty acid synthesis, which is mediated largely by sterol regulatory element-binding protein-1c (SREBP-1c). Paradoxically, an improved hepatic lipid profile by LXR was observed in mice fed a Western high fat (HF) diet. To explore the underlying mechanism, we administered mice normal chow or an HF diet and overexpressed LXR alpha in the liver. The HF diet with tail-vein injection of adenovirus of LXR alpha increased the expression of LXR-targeted genes involved in cholesterol reverse transport but not those involved in fatty acid synthesis. A similar effect was also observed with the use of 22R-hydroxycholesterol, an LXR ligand, in cultured hepatocytes. Consequently, SREBP-1c maturation was inhibited by the HF diet, which resulted from the induction of Insig-2a. Importantly, increased cholesterol level suppressed the expression of 2,3-oxidosqualene cyclase (OSC), which led to an increase in endogenous LXR ligand(s). Furthermore, siRNA-mediated knockdown of OSC expression enhanced LXR activity and selectively up-regulated LXR-targeted genes involved in cholesterol reverse transport. Thus, down-regulation of OSC may account for a novel mechanism underlying the LXR-mediated lipid metabolism in the liver of mice fed an HF diet.

语种: 英语
所属项目编号: HL77448 ; 30570713 ; 30630032 ; 30890040 ; 2006BC503802
项目资助者: National Institutes of Health ; National Natural Science Foundation of China ; Major National Basic Research Grant of China
WOS记录号: WOS:000263742700025
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56558
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China
2.Peking Univ, Inst Cardiovasc Res, Beijing 100083, Peoples R China
3.Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA

Recommended Citation:
Dang, Huaixin,Liu, Yan,Pang, Wei,et al. Suppression of 2,3-Oxidosqualene Cyclase by High Fat Diet Contributes to Liver X Receptor-alpha-mediated Improvement of Hepatic Lipid Profile[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(10):6218-6226.
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