title: Knockout of inositol-requiring enzyme 1α in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure.
abstract: Although numerous functions of inositol-requiring enzyme 1α (IRE1α) have been identified, a role of IRE1α in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1α specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, α-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1α in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1α is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Yuzhong
authors: Y
authors: Xiao
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Tingting
authors: T
authors: Xia
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Junjie
authors: J
authors: Yu
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Yalan
authors: Y
authors: Deng
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Hao
authors: H
authors: Liu
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Bin
authors: B
authors: Liu
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China.
authors: Shanghai
authors: S
authors: Chen
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China liuy@sibs.ac.cn.
authors: Yong
authors: Y
authors: Liu
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, The Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, People's Republic of China ffguo@sibs.ac.cn.
authors: Feifan
authors: 0000-0001-6748-4546
authors: F
authors: Guo
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism*; D004734:Energy Metabolism; D055786:Gene Knockout Techniques; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000517:prevention & control*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D022722:Thermogenesis; D013851:Thinness / Q000235:genetics; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: hypothalamus; inositol-requiring enzyme 1α; leptin sensitivity; obesity; pro-opiomelanocortin neurons