Yao Ting, Deng Zhuo, Gao Yong, Sun Jia, Kong Xingxing, Huang Yiru, He Zhenyan, Xu Yanchao, Chang Yongsheng, Yu Kai-Jiang, Findley Brianna G, Berglund Eric D, Wang Rui-Tao, Guo Hongbo, Chen Hong, Li Xu, Kaufman Randal J, Yan Jianqun, Liu Tiemin, Williams Kevin W
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Diabetes. 2017 Mar;66(3):663-673. doi: 10.2337/db16-0533. Epub 2016 Dec 27.
Whether neuronal inositol-requiring enzyme 1 () is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin ()-specific deficiency of accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of in neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of in neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that and associated molecular targets link ER stress in arcuate neurons to aspects of normal energy and glucose homeostasis.
神经元肌醇需求酶1（ ）是否为能量平衡和葡萄糖稳态的正常调节所必需尚不清楚。我们发现，促肾上腺皮质激素原（ ）特异性缺乏 会加速饮食诱导的肥胖，并伴有能量消耗减少。这种低代谢表型包括对饮食和寒冷暴露的产热反应缺陷以及白色脂肪组织的“米色化”。我们还证明， 神经元中 的缺失会损害全身葡萄糖和胰岛素耐受性以及肝脏胰岛素敏感性。在细胞水平上， 神经元中 的缺失会升高下丘脑内质网（ER）应激，并使 神经元易患瘦素和胰岛素抵抗。总之，目前的研究扩展并证实了以下结论： 和相关分子靶点将弓状 神经元中的内质网应激与正常能量和葡萄糖稳态的各个方面联系起来。
