Impact of life under hypoxia on gene expression in mice

Mountain dwellers show a lower prevalence of diabetes, which among countless other factors could be due to lower partial oxygen pressure at high altitude. The present study was to investigate in an experimental setting, if and how reduced oxygen availability affects blood glucose. For hypothesis building, tissue samples were collected from obese mice on high fat diet, which were maintained under normal air (control) or exposed to normobaric hypoxia for three months. Tissue samples were collected and subjected to RNA sequencing and bioinformatics analysis. In a subsequent series of experiments, hypoxia-induced effects on fuel metabolism as well as the mechanism mediating such effects were studied. As compared to controls, hypoxia-treated mice showed reduced blood glucose in association with improved insulin sensitivity, which was the direct consequence of an erythropoietin-mediated increase in the hematocrit. Overall design: After 3 months on, male obese mice were fed high fat diet (60% of calories as fat). After three months, they were allocated to a hypoxia group (kept in a chamber under 10% oxygen) and a control group (kept at normal air and fed restrictedly so to obtain a mean weight curve as similar as possible to the curve of their hypoxia-exposed counterparts). After another three months, tissue samples were collected approximately 4 h after opening the hypoxia chamber.