Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and contributes to hepatic steatosis in diet-induced insulin-resistant mice
文献类型：期刊论文
| 作者 | Zhang, Feifei2; Hu, Zhimin2; Huo, Shaofeng2; Ma, Fengguang2; Cui, Aoyuan2; Xue, Yaqian2; Han, Yamei2; Gong, Qi2; Gao, Jing2; Lin, Xu2 |
| 刊名 | HEPATOLOGY
 |
| 出版日期 | 2018 |
| 卷号 | 68期号:4页码:1361-1375 |
| ISSN号 | 0270-9139 |
| DOI | 10.1002/hep.29926 |
| 文献子类 | Article |
| 英文摘要 | Insulin is critical for the regulation of de novo fatty acid synthesis, which converts glucose to lipid in the liver. However, how insulin signals are transduced into the cell and then regulate lipogenesis remains to be fully understood. Here, we identified CREB/ATF bZIP transcription factor (CREBZF) of the activating transcription factor/cAMP response element-binding protein (ATF/CREB) gene family as a key regulator for lipogenesis through insulin-Akt signaling. Insulin-induced gene 2a (Insig-2a) decreases during refeeding, allowing sterol regulatory element binding protein 1c to be processed to promote lipogenesis; but the mechanism of reduction is unknown. We show that Insig-2a inhibition is mediated by insulin-induced CREBZF. CREBZF directly inhibits transcription of Insig-2a through association with activating transcription factor 4. Liver-specific knockout of CREBZF causes an induction of Insig-2a and Insig-1 and resulted in repressed lipogenic program in the liver of mice during refeeding or upon treatment with streptozotocin and insulin. Moreover, hepatic CREBZF deficiency attenuates hepatic steatosis in high-fat, high-sucrose diet-fed mice. Importantly, expression levels of CREBZF are increased in livers of diet-induced insulin resistance or genetically obese ob/ob mice and humans with hepatic steatosis, which may underscore the potential role of CREBZF in the development of sustained lipogenesis in the liver under selective insulin resistance conditions. Conclusion: These findings uncover an unexpected mechanism that couples changes in extracellular hormonal signals to hepatic lipid homeostasis; disrupting CREBZF function may have the therapeutic potential for treating fatty liver disease and insulin resistance. (Hepatology 2018). |
| 学科主题 | Gastroenterology & Hepatology |
| WOS关键词 | UNFOLDED PROTEIN RESPONSE ; FATTY-ACID SYNTHESIS ; TRANSCRIPTION FACTOR ; RECEPTOR-ALPHA ; LIVER-DISEASE ; CHOLESTEROL ; ELEMENT ; PATHWAYS ; ZHANGFEI ; ATHEROSCLEROSIS |
| 语种 | 英语 |
| WOS记录号 | WOS:000446431700016 |
| 出版者 | WILEY |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/749]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China; 2.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, Shanghai, Peoples R China; 3.Shenzhen Univ, Coll Life Sci & Oceanog, Shenzhen, Guangdong, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China; 5.Fudan Inst Metab Dis, Shanghai, Peoples R China; 6.Zhejiang Univ, Dept Pathol & Pathophysiol, Sch Med, Hangzhou, Zhejiang, Peoples R China; 7.Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Metab & Bariatr Surg, Shanghai, Peoples R China; 8.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China; 9.Univ Louisville, Dept Pediat, Wendy L Novak Diabet Care Ctr, Pediat Res Inst, Louisville, KY 40292 USA; 10.Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, Feifei,Hu, Zhimin,Huo, Shaofeng,et al. Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and contributes to hepatic steatosis in diet-induced insulin-resistant mice[J]. HEPATOLOGY,2018,68(4):1361-1375. |
| APA | Zhang, Feifei.,Hu, Zhimin.,Huo, Shaofeng.,Ma, Fengguang.,Cui, Aoyuan.,...&,.(2018).Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and contributes to hepatic steatosis in diet-induced insulin-resistant mice.HEPATOLOGY,68(4),1361-1375. |
| MLA | Zhang, Feifei,et al."Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and contributes to hepatic steatosis in diet-induced insulin-resistant mice".HEPATOLOGY 68.4(2018):1361-1375. |
入库方式： OAI收割
来源：上海营养与健康研究所
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