Reduced Oxygenation in Human Obese Adipose Tissue Is Associated with Impaired Insulin Suppression of Lipolysis

Context: Adipose tissue in obese individuals is characterized by reduced capillary density and reduced oxygenation. Objective: Our objective was to test whether hypoxia is associated with reduced antilipolytic effect of insulin. Participants, Design, and Setting: Twenty-one lean and obese individuals participated in this cross-sectional study at a university-based clinical research center. Intervention: 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). Main Outcome Measure: In situ ATpO2 was evaluated. Results: 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). Conclusion: These results indicate that low capillary density and ATpO2 in AT are potentially upstream causes of AT dysfunction.