Xiao Yuzhong, Xia Tingting, Yu Junjie, Deng Yalan, Liu Hao, Liu Bin, Chen Shanghai, Liu Yong, Guo Feifan
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.
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
Open Biol. 2016 Aug;6(8). doi: 10.1098/rsob.160131.
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.
尽管肌醇需求酶1α（IRE1α）的众多功能已被确定，但IRE1α在下丘脑弓状核促黑素细胞激素原（POMC）神经元中的作用仍大多未知。在此，我们发现POMC神经元中特异性缺失IRE1α的小鼠（PIKO）体型瘦，对高脂饮食诱导的肥胖、肥胖相关的胰岛素抵抗、肝脏脂肪变性和瘦素抵抗具有抗性。此外，PIKO小鼠能量消耗更高，这可能是由于棕色脂肪组织产热增加所致。另外，PIKO小鼠下丘脑中α-促黑素细胞激素的产生增加。这些结果表明，POMC神经元中的IRE1α在肥胖及肥胖相关代谢紊乱的调节中起关键作用。我们的结果还表明，IRE1α不仅是一种内质网应激传感器，也是肥胖及肥胖相关代谢疾病的一个新的潜在治疗靶点。
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