title: The local corticotropin-releasing hormone receptor 2 signalling pathway partly mediates hypoxia-induced increases in lipolysis via the cAMP-protein kinase A signalling pathway in white adipose tissue.
abstract: Our objective was to investigate the mechanisms by which the endogenous CRHR2 in white adipose tissue (WAT) regulates metabolic activities associated with lipogenesis and lipolysis under continuous exposure to hypoxia. We found that hypobaric hypoxia at a simulated altitude of 5000 m significantly reduced the body weight, food intake, and WAT mass of rats. Hypoxia also accelerated lipolysis and suppressed lipogenesis in WAT. Pretreatment with astressin 2B, a selective CRHR2 antagonist, partly but significantly attenuated the hypoxia-induced reductions in body weight and WAT mass by blocking the cAMP-protein kinase A (PKA)-hormone-sensitive lipase (HSL)/perilipin signalling pathway. Astressin 2B treatment failed to attenuate hypoxia induced lipogenic inhibition. In conclusion, activation of endogenous WAT Ucn2/3 autocrine/paracrine pathway was involved in hypoxia induced lipolysis via CRHR2 - cAMP-PKA signalling pathway. This study provides the novel understanding of local CRHR2 signaling pathway playing important role in WAT loss and lipid metabolism under hypoxia.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, People's Republic of China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, People's Republic of China.
authors.forename: Mintao
authors.initials: M
authors.lastname: Song
authors.affiliation: Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Xuequn
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang University, Hangzhou, People's Republic of China. Electronic address: dujz@zju.edu.cn.
authors.forename: Jizeng
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, People's Republic of China. Electronic address: xuchengli@pumc.edu.cn.
authors.forename: Chengli
authors.initials: C
authors.lastname: Xu
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects; D000531:Altitude; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
chemical_list: C101531:CRF receptor type 2; D005227:Fatty Acids; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018019:Receptors, Corticotropin-Releasing Hormone; D014280:Triglycerides; C528574:astressin-2B; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Corticotropin-releasing hormone receptor 2; Hypoxia; Lipolysis; White adipose tissue