title: Ire1αinPomcNeurons Is Required for Thermogenesis and Glycemia.
abstract: Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency ofIre1αaccelerated 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 ofIre1αinPomcneurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion ofIre1αinPomcneurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposedPomcneurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions thatIre1α-Xbp1sand associated molecular targets link ER stress in arcuatePomcneurons to aspects of normal energy and glucose homeostasis.
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Yao
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Gynecology, Shaanxi Provincial People's Hospital, Shaanxi, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.|National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Kong
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhenyan
authors.initials: Z
authors.lastname: He
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Kai-Jiang
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Division of Metabolic Mechanisms of Disease, Advanced Imaging Research Center and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Brianna G
authors.initials: BG
authors.lastname: Findley
authors.affiliation: Division of Metabolic Mechanisms of Disease, Advanced Imaging Research Center and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Berglund
authors.affiliation: Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Rui-Tao
authors.initials: RT
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA.
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China kevin.williams@utsouthwestern.edu tiemin.liu@utsouthwestern.edu jqyan@xjtu.edu.cn.
authors.forename: Jianqun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX kevin.williams@utsouthwestern.edu tiemin.liu@utsouthwestern.edu jqyan@xjtu.edu.cn.|Department of Intensive Care Unit, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX kevin.williams@utsouthwestern.edu tiemin.liu@utsouthwestern.edu jqyan@xjtu.edu.cn.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D003080:Cold Temperature; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000235:genetics*; D000071717:X-Box Binding Protein 1 / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D020738:Leptin; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D011333:Pro-Opiomelanocortin; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D005947:Glucose