Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease

被引：28

作者：

Chen, Shuai ^{[1
]}

Kang, Yujia ^{[1
]}

Sun, Yan ^{[1
]}

Zhong, Yanhong ^{[1
]}

Li, Yanli ^{[1
]}

Deng, Lijuan ^{[1
]}

Tao, Jin ^{[1
]}

Li, Yang ^{[1
]}

Tian, Yingpu ^{[1
]}

Zhao, Yinan ^{[1
]}

Cheng, Jianghong ^{[1
]}

Liu, Wenjie ^{[1
]}

Feng, Gen-Sheng ^{[2
,3
]}

Lu, Zhongxian ^{[1
]}

机构：

[1] Xiamen Univ, State Key Lab Cellular Stress Biol, Sch Pharmaceut Sci, Xiamen 361005, Fujian, Peoples R China

[2] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2016年 / 8卷 / 06期

基金：

中国国家自然科学基金;

关键词：

alcoholic fatty liver disease; non-alcoholic fatty liver disease; knockout mouse; disease-associated protein; therapeutic target; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; ENERGY-BALANCE; PROTEINS; PATHWAY; SHP2; ACTIVATION; LEPTIN; LEADS;

D O I：

10.1093/jmcb/mjw028

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders. The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors. In this study, we investigated the role of a signaling adaptor protein, GRB2-associated-binding protein 2 (Gab2), in fatty liver using an animal disease model. Gab2 expression in hepatocytes responded to various disease factor stimulations, and Gab2 knockout mice exhibited resistance to fat-induced obesity, fat-or alcohol-stimulated hepatic steatosis, as well as methionine and choline deficiency-induced steatohepatitis. Concordantly, the forced expression or knockdown of Gab2 enhanced or diminished oleic acid (OA)-or ethanol-induced lipid production in hepatocytes in vitro, respectively. During lipid accumulation in hepatocytes, both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT, ERK, and Stat3. Therefore, Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver. Our research provides a novel potential target for the prevention and intervention of fatty liver disease.

引用

页码：492 / 504

页数：13

共 40 条

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