Hypoxia exposure alleviates impaired muscular metabolism, glucose tolerance, and aerobic capacity in apelin‐knockout mice

High altitude hypoxia adaptation can improve glucose tolerance in people with metabolic syndrome and type 2 diabetes (T2D). Apelin is an endogenous ligand of the G protein‐coupled receptor APJ and has possible roles in energy metabolism. Apelin‐null mice have been reported to exhibit impaired insulin sensitivity, which can be reversed by supplementation of exogenous apelin. Here, we examined the effects of 4 weeks’ intermittent hypoxia exposure on physiological and biochemical variables in apelin knockout (KO) mice. Apelin KO mice exhibited decreased expression of substrate metabolism‐associated genes/proteins, impaired glucose tolerance, and reduced exercise capacity compared to wild‐type mice, and all of these effects were rescued by hypoxia. These findings suggest that hypoxia intervention may possibly be able to alleviate metabolic conditions caused by genetic defects.