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Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.

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资源类型：
Pubmed体系：
作者：
Qin Tang[1,2] * ; Yong Gao[4] * ; Qinhui Liu[2] ; Xuping Yang[1,2] ; Tong Wu[1,2] ; Cuiyuan Huang[1,2] ; Ya Huang[1,2] ; Jinhang Zhang[1,2] ; Zijing Zhang[1,2] ; Rui Li[1,2] ; Shiyun Pu[1,2] ; Guorong Zhang[1,2] ; Yingnan Zhao[1,2] ; Jian Zhou[1,2] ; Hui Huang[1,2] ; Yanping Li[1,2] ; Wei Jiang[3] ; Yongsheng Chang[5,*2] ; Jinhan He[1,2,*1] ;
机构： [1]Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [2]Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [3]Molecular Medicine Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [4]Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China [5]Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China
出处：
DOI： 10.1016/j.molmet.2020.100994

关键词： Sirt6 POMC neurons Leptin sensitivity Obesity Energy balance Sympathetic nervous system

摘要：
Sirt6 is an essential regulator of energy metabolism in multiple peripheral tissues. However, the direct role of Sirt6 in the hypothalamus, specifically pro-opiomelanocortin (POMC) neurons, controlling energy balance has not been established. Here, we aimed to determine the role of Sirt6 in hypothalamic POMC neurons in the regulation of energy balance and the underlying mechanisms. For overexpression studies, the hypothalamic arcuate nucleus (ARC) of diet-induced obese mice was targeted bilaterally and adenovirus was delivered by using stereotaxic apparatus. For knockout studies, the POMC neuron-specific Sirt6 knockout mice (PKO mice) were generated. Mice were fed with chow diet or high-fat diet, and body weight and food intake were monitored. Whole-body energy expenditure was determined by metabolic cages. Parameters of body composition and glucose/lipid metabolism were evaluated. Sirt6 overexpression in the ARC ameliorated diet-induced obesity. Conversely, selective Sirt6 ablation in POMC neurons predisposed mice to obesity and metabolic disturbances. PKO mice showed an increased fat mass and food intake, while the energy expenditure was decreased. Mechanistically, Sirt6 could modulate leptin signaling in hypothalamic POMC neurons, with Sirt6 deficiency impairing leptin-induced phosphorylation of signal transducer and activator of transcription 3. The effects of leptin on reducing food intake and body weight and leptin-stimulated lipolysis were also impaired. Moreover, Sirt6 inhibition diminished the leptin-induced depolarization of POMC neurons. Our results reveal a key role of Sirt6 in POMC neurons against energy imbalance, suggesting that Sirt6 is an important molecular regulator for POMC neurons to promote negative energy balance. Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.

基金：
This work was supported by the National Natural Science Foundation of China (81930020, 81873662, and 81870599), research funding from Sichuan Province (2018SZ0158), China Postdoctoral Fellowship (2017M612981), Young Scientist Fellowship of Sichuan University (2017SCU11026), and Postdoctoral Fellowship of Sichuan University (2017SCU12036).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类 | 1 区 医学
小类 | 2 区 内分泌学与代谢
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 内分泌学与代谢
第一作者：
第一作者机构： [1]Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [2]Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [2]Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China [5]Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China [*1]Department of Pharmacy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China. [*2]Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China.
推荐引用方式(GB/T 7714)：
Qin Tang,Yong Gao,Qinhui Liu,et al.Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.[J].Molecular metabolism.2020,37:100994.doi:10.1016/j.molmet.2020.100994.
APA：
Qin Tang,Yong Gao,Qinhui Liu,Xuping Yang,Tong Wu...&Jinhan He.(2020).Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling..Molecular metabolism,37,
MLA：
Qin Tang,et al."Sirt6 in pro-opiomelanocortin neurons controls energy metabolism by modulating leptin signaling.".Molecular metabolism 37.(2020):100994

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