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学科主题基础医学
Suppression of 2,3-Oxidosqualene Cyclase by High Fat Diet Contributes to Liver X Receptor-alpha-mediated Improvement of Hepatic Lipid Profile
Dang, Huaixin1; Liu, Yan1; Pang, Wei1; Li, Chenghong1; Wang, Nanping2; Shyy, John Y. -J.3; Zhu, Yi1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2009-03-06
DOI10.1074/jbc.M803702200
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
WOS记录号WOS:000263742700025
项目编号HL77448 ; 30570713 ; 30630032 ; 30890040 ; 2006BC503802
资助机构National Institutes of Health ; National Natural Science Foundation of China ; Major National Basic Research Grant of China
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56558
专题北京大学基础医学院_心血管所
北京大学基础医学院
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
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GB/T 7714
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.
APA Dang, Huaixin.,Liu, Yan.,Pang, Wei.,Li, Chenghong.,Wang, Nanping.,...&Zhu, Yi.(2009).Suppression of 2,3-Oxidosqualene Cyclase by High Fat Diet Contributes to Liver X Receptor-alpha-mediated Improvement of Hepatic Lipid Profile.JOURNAL OF BIOLOGICAL CHEMISTRY,284(10),6218-6226.
MLA Dang, Huaixin,et al."Suppression of 2,3-Oxidosqualene Cyclase by High Fat Diet Contributes to Liver X Receptor-alpha-mediated Improvement of Hepatic Lipid Profile".JOURNAL OF BIOLOGICAL CHEMISTRY 284.10(2009):6218-6226.
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