期刊
ENDOCRINOLOGY
卷 154, 期 5, 页码 1722-1730出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2012-2009
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资金
- National Research Foundation [2012R1A2A2A01043867, 2012R1A1A1010047]
- National Research Foundation (World Class University Program Grant) [R32-10064]
- National Research Foundation (Future-Based Technology Development Program Bio Field Grant) [2011-0019514]
- Ministry of Education, Science, and Technology
- Korea Health Technology Research and Development Project from the Ministry of Health and Welfare, Republic of Korea [A111345]
- National Research Foundation of Korea [2012R1A1A1010047] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hepatic steatosis is emerging as the most important cause of chronic liver disease and is associated with the increasing incidence of obesity with insulin resistance. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver. Hyperinsulinemia induces SREBP-1c transcription through liver X receptor (LXR), specificity protein 1, and SREBP-1c itself. Clusterin, an 80-kDa disulfide-linked heterodimeric protein, has been functionally implicated in several physiological processes including lipid transport; however, little is known about its effect on hepatic lipogenesis. The present study examined whether clusterin regulates SREBP-1c expression and lipid accumulation in the liver. Adenovirus-mediated overexpression of clusterin inhibited insulin-or LXR agonist-stimulated SREBP-1c expression in cultured liver cells. In reporter assays, clusterin inhibited SREBP-1c promoter activity. Moreover, adenovirus-mediated overexpression of clusterin in the livers of mice fed a high-fat diet inhibited hepatic steatosis through the inhibition of SREBP-1c expression. Reporter and gel shift assays showed that clusterin inhibits SREBP-1c expression via the repression of LXR and specificity protein 1 activity. This study shows that clusterin inhibits hepatic lipid accumulation through the inhibition of SREBP-1c expression and suggests that clusterin is a negative regulator of SREBP-1c expression and hepatic lipogenesis. (Endocrinology 154: 1722-1730, 2013)
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