Deletion of ATF4 in AgRP Neurons Promotes Fat Loss Mainly via Increasing Energy Expenditure
文献类型：期刊论文
| 作者 | Deng, Jiali3; Yuan, Feixiang3; Guo, Yajie3; Xiao, Yuzhong3; Niu, Yuguo3; Deng, Yalan3; Chen, Shanghai3; Guo, Feifan3; Han, Xiao2; Guan, Youfei1 |
| 刊名 | DIABETES
 |
| 出版日期 | 2017 |
| 卷号 | 66期号:3页码:640-650 |
| 关键词 | Phosphosite Phosphopeptide Phosphopeptide mass |
| ISSN号 | 0012-1797 |
| DOI | 10.2337/db16-0954 |
| 文献子类 | Article |
| 英文摘要 | Although many functions of activating transcription factor 4 (ATF4) are identified, a role of ATF4 in the hypothalamus in regulating energy homeostasis is unknown. Here, we generated adult-onset agouti-related peptide neuron-specific ATF4 knockout (AgRP-ATF4 KO) mice and found that these mice were lean, with improved insulin and leptin sensitivity and decreased hepatic lipid accumulation. Furthermore, AgRP-ATF4 KO mice showed reduced food intake and increased energy expenditure, mainly because of enhanced thermogenesis in brown adipose tissue. Moreover, AgRP-ATF4 KO mice were resistant to high-fat diet-induced obesity, insulin resistance, and liver steatosis and maintained at a higher body temperature under cold stress. Interestingly, the expression of FOXO1 was directly regulated by ATF4 via binding to the cAMP-responsive element site on its promoter in hypothalamic GT1-7 cells. Finally, Foxo1 expression was reduced in the arcuate nucleus (ARC) of the hypothalamus of AgRP-ATF4 KO mice, and adenovirus-mediated overexpression of FOXO1 in ARC increased the fat mass in AgRP-ATF4 KO mice. Collectively, our data demonstrate a novel function of ATF4 in AgRP neurons of the hypothalamus in energy balance and lipid metabolism and suggest hypothalamic ATF4 as a potential drug target for treating obesity and its related metabolic disorders. |
| 学科主题 | Endocrinology & Metabolism |
| WOS关键词 | NERVOUS-SYSTEM CONTROL ; HEPATIC INSULIN-RESISTANCE ; REGULATES FOOD-INTAKE ; TRANSCRIPTION FACTOR ; LIPID-METABOLISM ; GLUCOSE-HOMEOSTASIS ; LEPTIN SENSITIVITY ; BODY-WEIGHT ; FOXO1 ; THERMOGENESIS |
| 语种 | 英语 |
| WOS记录号 | WOS:000394634100010 |
| 出版者 | AMER DIABETES ASSOC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/940]  |
| 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.Dalian Med Univ, Adv Inst Med Sci, Dalian, Peoples R China, 2.Nanjing Med Univ, Jiangsu Diabet Ctr, Key Lab Human Funct Genom Jiangsu Prov, Nanjing, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Grad Sch, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Deng, Jiali,Yuan, Feixiang,Guo, Yajie,et al. Deletion of ATF4 in AgRP Neurons Promotes Fat Loss Mainly via Increasing Energy Expenditure[J]. DIABETES,2017,66(3):640-650. |
| APA | Deng, Jiali.,Yuan, Feixiang.,Guo, Yajie.,Xiao, Yuzhong.,Niu, Yuguo.,...&,.(2017).Deletion of ATF4 in AgRP Neurons Promotes Fat Loss Mainly via Increasing Energy Expenditure.DIABETES,66(3),640-650. |
| MLA | Deng, Jiali,et al."Deletion of ATF4 in AgRP Neurons Promotes Fat Loss Mainly via Increasing Energy Expenditure".DIABETES 66.3(2017):640-650. |
入库方式： OAI收割
来源：上海营养与健康研究所
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