Effect of hypoxia on caveolae-related protein expression and insulin signaling in adipocytes

Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes. Furthermore, 48 h of hypoxia reduced insulin-induced glucose uptake while increased basal glucose uptake. This result was consistent with the upregulation of glucose transporter GLUT1 and the downregulation of GLUT4, which also showed defective translocation to plasma membrane when adipocytes were stimulated with insulin. In addition, the expression of caveolae-related proteins was reduced by hypoxia and chromatin immunoprecipitation assay demonstrated that Cav-1 transcription was directly regulated by HIF-1. These results strengthen the role of caveolae in insulin signaling and help to explain adipocyte response to hypoxia.