Year: 2016
Type: article
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 of Ire1α 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 Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.
Source: Diabetes
DOI: 10.2337/db16-0533
Institutions: The University of Texas Southwestern Medical Center, Xi'an Jiaotong University, Shaanxi Provincial People's Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, Zhujiang Hospital, Southern Medical University, Beth Israel Deaconess Medical Center, Harvard University, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, First Affiliated Hospital of Xi'an Jiaotong University, Sanford Burnham Prebys Medical Discovery Institute
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: Mouse Phenotype Core, Project 9 of 10, G3009786373, G3145668905, The Role of IRF4 in Exercise Induced Thermogenesis, Modifiers of Proinsulin Influence T2D Susceptibility, G3609464687, Novel Insulin-Independent Gluco-Regulatory Mechanisms, G5034259937, G6725775549, Homeostatic Role of IRE1a-XBP1-PDI1 in Hepatic Lipid Metabolism, Taskforce for Obesity Research at Southwestern (TORS), Central Mechanisms Regulating Acute Leptin and Insulin Signaling, G7544601775, Role of the Unfolded Protein Response in Beta Cell
OpenAlex ID: W2567126696