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

•Hypoxia accelerated lipolysis and suppresses lipogenesis in WAT.•Hypoxia activated the local Ucn2/Ucn3 – CRHR2 expression in WAT.•Local CRHR2 in WAT has autocrine/paracrine function in regulating lipolysis via cAMP–PKA pathway. 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 5000m 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.