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MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4

文献类型:期刊论文

作者Li, Kai; Zhang, Jin; Yu, Junjie; Liu, Bin; Guo, Yajie; Deng, Jiali; Chen, Shanghai(陈上海); Wang, Chunxia; Guo, Feifan(郭非凡)
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2015
卷号290期号:13页码:8185-8195
通讯作者Guo, FF (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文摘要Although the gluconeogenesis pathway is already a target for the treatment of type 2 diabetes, the potential role of microRNAs (miRNAs) in gluconeogenesis remains unclear. Here, we investigated the physiological functions of miR-214 in gluconeogenesis. The expression of miR-214 was suppressed by glucagon via protein kinase A signaling in primary hepatocytes, and miR-214 was down-regulated in the livers of fasted, high fat diet-induced diabetic and leptin receptor-mutated (db/db) mice. The overexpression of miR-214 in primary hepatocytes suppressed glucose production, and silencing miR-214 reversed this effect. Gluconeogenesis was suppressed in the livers of mice injected with an adenovirus expressing miR-214 (Ad-miR-214). Additionally, Ad-miR-214 alleviated high fat diet-induced elevation of gluconeogenesis and hyperglycemia. Furthermore, we found that activating transcription factor 4 (ATF4), a reported target of miR-214, can reverse the suppressive effect of miR-214 on gluconeogenesis in primary hepatocytes, and this suppressive effect was blocked in liver-specific ATF4 knock-out mice. ATF4 regulated gluconeogenesis via affecting forkhead box protein O1(FOXO1) transcriptional activity. Finally, liver-specific miR214 transgenic mice exhibited suppressed gluconeogenesis and reduced expression of ATF4, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in liver. Taken together, our results suggest that the miR-214-ATF4 axis is a novel pathway for the regulation of hepatic gluconeogenesis.
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]HIGH-FAT DIET ; REGULATES GLUCOSE-METABOLISM ; INDUCED HEPATIC STEATOSIS ; PERFUSED-RAT-LIVER ; PHOSPHOENOLPYRUVATE CARBOXYKINASE ; DIABETES-MELLITUS ; COACTIVATOR PGC-1 ; LIPID-METABOLISM ; ACUTE EXERCISE ; EXPRESSION
收录类别SCI
语种英语
WOS记录号WOS:000351662600016
公开日期2016-02-26
版本出版稿
源URL[http://202.127.25.144/handle/331004/420]  
专题中国科学院上海生命科学研究院营养科学研究所_代谢的遗传与营养调控研究组
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GB/T 7714
Li, Kai,Zhang, Jin,Yu, Junjie,et al. MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(13):8185-8195.
APA Li, Kai.,Zhang, Jin.,Yu, Junjie.,Liu, Bin.,Guo, Yajie.,...&Guo, Feifan.(2015).MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4.JOURNAL OF BIOLOGICAL CHEMISTRY,290(13),8185-8195.
MLA Li, Kai,et al."MicroRNA-214 Suppresses Gluconeogenesis by Targeting Activating Transcriptional Factor 4".JOURNAL OF BIOLOGICAL CHEMISTRY 290.13(2015):8185-8195.

入库方式: OAI收割

来源:上海营养与健康研究所

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