Reduced Adipose Tissue Oxygenation in Human Obesity - Evidence for Rarefaction, Macrophage Chemotaxis and Inflammation without an Angiogenic Response

Abstract

Objective: Based on rodent studies, we examined the hypothesis that increased adipose tissue mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration and inflammation.

Research Design and Methods: Oxygen partial pressure [AT pO₂] and temperature [AT temperature] in abdominal adipose tissue [9 lean, 12 overweight/obese men and women] was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by DEXA, insulin sensitivity by hyperinsulinemic euglycemic clamp. Abdominal subcutaneous tissue was used for staining, qRT-PCR and chemokine secretion assay.

Results: AT pO₂ was lower in overweight/obese as compared to lean [47 ± 10.6 vs. 55 ± 9.1 mm Hg], however this level of pO₂ did not activate the classic hypoxia targets [PDK1, VEGF]. AT pO₂ was negatively correlated with % fat [R=−0.50, p<0.05]. Compared to lean, overweight/obese subjects had 44% lower capillary density and 58% lower Vascular Endothelial Growth Factor [VEGF] suggesting adipose tissue rarefaction [capillary dropout]. This might be due to lower PPARγ1 and higher collagenVI mRNA expression, which correlated with AT pO₂ [p<0.05]. Of clinical importance, AT pO₂ negatively correlated with CD68 mRNA and MIP1α secretion [R=−0.58, R=−0.79, p<0.05], suggesting that lower AT pO₂ could drive AT inflammation in obesity.

Conclusions: Adipose tissue rarefaction might lie upstream of both low AT pO₂ and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional adipose tissue found in obesity.