Reduced Adipose Tissue Oxygenation in Human Obesity

TLDR

Based on rodent studies, increased adipose tissue mass in obesity without adequate vascular support may lead to hypoxia, macrophage infiltration, and inflammation. The study aimed to test whether excess adipose tissue in obese individuals, lacking sufficient vascularization, results in tissue hypoxia and subsequent inflammatory responses. Researchers measured abdominal adipose tissue oxygen pressure and temperature with a polarographic Clark electrode in 9 lean and 12 overweight/obese adults, assessed body composition by DXA, insulin sensitivity by hyperinsulinemic‑euglycemic clamp, and performed staining, RT‑PCR, and chemokine secretion assays on subcutaneous tissue. Results showed that overweight/obese subjects had lower AT pO₂, reduced capillary density and VEGF, and higher inflammatory markers, with pO₂ inversely correlated with body fat, capillary loss, collagen VI, and macrophage‑associated cytokines, suggesting that adipose tissue rarefaction drives hypoxia and inflammation in obesity.

Abstract

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) 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 AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α 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 AT found in obesity.