Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 392, Issue 1-2, Pages 106-114Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2014.05.012
Keywords
Hypoxia; Corticotropin-releasing hormone receptor 2; White adipose tissue; Lipolysis
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Funding
- Ministry of Science and Technology of China
- National Basic Research Program of China (973 Program) [2012CB518200]
- Chinese Polar Environment Comprehensive Investigation & Assessment Programs [CHINARE2013-02-01]
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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. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
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