Reduced adipose tissue oxygenation in human obesity evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response
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 pO 2) 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 pO 2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO 2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO 2 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 pO 2 (P < 0.05). Of clinical importance, AT pO 2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R =-0.58, R =-0.79, P < 0.05), suggesting that lower AT pO 2 could drive AT inflammation in obesity. CONCLUSIONS-Adipose tissue rarefaction might lie upstream of both low AT pO 2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity. © 2009 by the American Diabetes Association.
Publication Source (Journal or Book title)
Pasarica, M., Sereda, O., Redman, L., Albarado, D., Hymel, D., Roan, L., Rood, J., Burk, D., & Smith, S. (2009). Reduced adipose tissue oxygenation in human obesity evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes, 58 (3), 718-725. https://doi.org/10.2337/db08-1098