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学科主题基础医学
Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice
Guo, Feng1; Ma, Yinyan1,3; Kadegowda, Anil K. G.3; Xie, Ping1; Liu, George4,5; Liu, Xiuli6; Miao, Hongming3; Ou, Juanjuan3; Su, Xiong7,8,9,10; Zheng, Zhenlin2; Xue, Bingzhong11; Shi, Hang11; Yu, Liqing1,3
关键词Triglyceride Hydrolysis Lipase Fatty Liver Cgi-58
刊名JOURNAL OF LIPID RESEARCH
2013-08-01
DOI10.1194/jlr.M035519
54期:8页:2109-2120
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]ADIPOSE TRIGLYCERIDE LIPASE ; NONALCOHOLIC FATTY LIVER ; LIPID STORAGE DISEASE ; CHANARIN-DORFMAN-SYNDROME ; HEPATIC INSULIN-RESISTANCE ; TRIACYLGLYCEROL LIPASE ; CGI-58 KNOCKDOWN ; ACID OXIDATION ; STEATOSIS ; LIPOLYSIS
英文摘要

Triglyceride (TG) accumulation in hepatocytes (hepatic steatosis) preludes the development of advanced nonalcoholic fatty liver diseases (NAFLDs) such as steatohepatitis, fibrosis, and cirrhosis. Mutations in human Comparative Gene Identification-58 (CGI-58) cause cytosolic TG-rich lipid droplets to accumulate in almost all cell types including hepatocytes. However, it is unclear if CGI-58 mutation causes hepatic steatosis locally or via altering lipid metabolism in other tissues. To directly address this question, we created liver-specific CGI-58 knockout (LivKO) mice. LivKO mice on standard chow diet displayed microvesicular and macrovesicular panlobular steatosis, and progressed to advanced NAFLD stages over time, including lobular inflammation and centrilobular fibrosis. Compared with CGI-58 floxed control littermates, LivKO mice showed 8-fold and 52-fold increases in hepatic TG content, which was associated with 40% and 58% decreases in hepatic TG hydrolase activity at 16 and 42 weeks, respectively. Hepatic cholesterol also increased significantly in LivKO mice. At 42 weeks, LivKO mice showed increased hepatic oxidative stress, plasma aminotransferases, and hepatic mRNAs for genes involved in fibrosis and inflammation, such as alpha-smooth muscle actin, collagen type 1 alpha 1, tumor necrosis factor alpha, and interleukin-1 beta. In conclusion, CGI-58 deficiency in the liver directly causes not only hepatic steatosis but also steatohepatitis and fibrosis.

语种英语
WOS记录号WOS:000321613300008
项目编号R01DK-085176
资助机构Wake Forest University Health Sciences ; University of Maryland ; National Institute of Diabetes and Digestive and Kidney Diseases
引用统计
被引频次:33[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/400002259/52354
专题北京大学基础医学院_心血管所
作者单位1.Washington Univ, Sch Med, St Louis, MO USA
2.Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
3.Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA
4.Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27109 USA
5.Wake Forest Univ, Sch Med, Dept Plast Surg, Winston Salem, NC 27109 USA
6.Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA
7.Peking Univ, Hlth Sci Ctr, Minist Educ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
8.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100871, Peoples R China
9.Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA
10.Washington Univ, Sch Med, Dept Physiol, St Louis, MO 63110 USA
11.Georgia State Univ, Dept Biol, Atlanta, GA USA
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Guo, Feng,Ma, Yinyan,Kadegowda, Anil K. G.,et al. Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice[J]. JOURNAL OF LIPID RESEARCH,2013,54(8):2109-2120.
APA Guo, Feng.,Ma, Yinyan.,Kadegowda, Anil K. G..,Xie, Ping.,Liu, George.,...&Yu, Liqing.(2013).Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice.JOURNAL OF LIPID RESEARCH,54(8),2109-2120.
MLA Guo, Feng,et al."Deficiency of liver Comparative Gene Identification-58 causes steatohepatitis and fibrosis in mice".JOURNAL OF LIPID RESEARCH 54.8(2013):2109-2120.
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