Decreased adipose tissue oxygenation is associated with insulin resistance in people with obesity

We evaluated the potential importance of adipose tissue (AT) oxygenation on AT biology and insulin sensitivity in people. AT oxygen partial pressure (pO2), branched chain amino acid (BCAA) catabolism and marker of inflammation were determined in three groups stratified by adiposity and insulin sensitivity: 1) metabolically-healthy lean (MHL); 2) metabolically-healthy obese (MHO); and 3) metabolically-unhealthy obese (MUO). AT pO2 progressively declined from the MHL to the MHO to the MUO group, and was positively associated with hepatic and whole-body insulin sensitivity. AT pO2 was positively associated with AT expression of genes involved in BCAA catabolism and negatively associated with plasma BCAA concentrations. Although AT pO2 was negatively associated with AT markers of inflammation, it was not associated with plasma adipokine concentrations. These results support the notion that reduced AT pO2 in people with obesity contributes to insulin resistance by decreasing AT BCAA catabolism and thereby increasing plasma BCAA concentrations. We obtained subcutaneous adipose tissue samples from people who were metabolically-healthy lean (MHL), metabolically-healthy obese (MHO), and metabolically-unhealthy obese (MUO) (n=45). We then identified genes that were significantly associated with AT oxygen content based on data obtained from RNA-seq.