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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00704197.

Figure 1

Pearson correlation between suppression of lipolysis and insulin sensitivity for glucose disposal (A); AT oxygenation, ATpO₂ (B); VEGF (C); and capillary density by image analysis (D). Males are represented by squares and females by circles: white for lean, gray for obese without type 2 diabetes, and black for obese with type 2 diabetes. AU, Arbitrary units.