AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue
文献类型：期刊论文
| 作者 | Wu, Lingyan1,2; Zhang, Lina2; Li, Bohan1,2; Jiang, Haowen3; Duan, Yanan3; Xie, Zhifu1,2; Shuai, Lin1,2; Li, Jia2 ; Li, Jingya2
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| 刊名 | FRONTIERS IN PHYSIOLOGY
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| 出版日期 | 2018-02-21 |
| 卷号 | 9 |
| ISSN号 | 1664-042X |
| 关键词 | AMP-activated protein kinase thermogenesis energy metabolism A-769662 white adipose browning PGC-1 alpha |
| DOI | 10.3389/fphys.2018.00122 |
| 文献子类 | Article |
| 英文摘要 | Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK alpha 1/alpha 2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a beta 3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPK a induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively, whereas chronic AMPK activation by A-769662 promoted WAT browning in inguinal WAT and protected against HFD-induced obesity and related metabolic dysfunction. These findings reveal a vital role for adipocyte AMPK in regulating the browning process in inguinal WAT and in maintaining energy homeostasis, which suggests that the targeted activation of adipocyte AMPK may be a promising strategy for anti-obesity therapy. |
| WOS关键词 | SKELETAL-MUSCLE ; INSULIN-RESISTANCE ; FATTY-ACID ; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE ; ADIPOCYTE DIFFERENTIATION ; PHOSPHORYLATION SITES ; BROWN ADIPOGENESIS ; MICE ; LEPTIN ; HOMEOSTASIS |
| 资助项目 | National Key Research and Development[2016YFC1305500] ; National Natural Science Foundation of China[81673493] ; National Natural Science Foundation of China[81673489] ; Shanghai Commission of Science and Technology[14431902800] ; Shanghai Commission of Science and Technology[16JC1405000] ; Shanghai Commission of Science and Technology[16430711700] |
| WOS研究方向 | Physiology |
| 语种 | 英语 |
| 出版者 | FRONTIERS MEDIA SA |
| WOS记录号 | WOS:000425644200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279892]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Li, Jingya |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 3.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Lingyan,Zhang, Lina,Li, Bohan,et al. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue[J]. FRONTIERS IN PHYSIOLOGY,2018,9. |
| APA | Wu, Lingyan.,Zhang, Lina.,Li, Bohan.,Jiang, Haowen.,Duan, Yanan.,...&Li, Jingya.(2018).AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue.FRONTIERS IN PHYSIOLOGY,9. |
| MLA | Wu, Lingyan,et al."AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue".FRONTIERS IN PHYSIOLOGY 9(2018). |
入库方式： OAI收割
来源：上海药物研究所
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