Reduced oxygenation in human obese adipose tissue is associated with impaired insulin suppression of lipolysis.

Adipose tissue in obese individuals is characterized by reduced capillary density and reduced oxygenation. Our objective was to test whether hypoxia is associated with reduced antilipolytic effect of insulin. Twenty-one lean and obese individuals participated in this cross-sectional study at a university-based clinical research center. In all subjects, in situ adipose tissue (AT) oxygenation [AT oxygen partial pressure (ATpO2)] was measured with a Clark electrode, insulin sensitivity as well as basal and insulin-suppressed lipolysis (continuous infusion of (2H5)glycerol) were measured during a euglycemic-hyperinsulinemic clamp, and abdominal sc AT biopsies were collected to assess fat cell size (Coulter counting of osmium-fixed cells), capillary density (by staining of histological sections), and gene expression (by quantitative RT-PCR). In situ ATpO2 was evaluated. The ability of insulin to suppress lipolysis (percent) was positively correlated with insulin sensitivity (r=0.43; P<0.05), ATpO2 (r=0.44; P<0.05), vascular endothelial growth factor mRNA (r=0.73; P<0.01), and capillary density (r=0.75; P<0.01). These results indicate that low capillary density and ATpO2 in AT are potentially upstream causes of AT dysfunction.