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.