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.


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 gamma1 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 1alpha 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.
Pasarica
Magdalena
M
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Sereda
Olga R
OR
Redman
Leanne M
LM
Albarado
Diana C
DC
Hymel
David T
DT
Roan
Laura E
LE
Rood
Jennifer C
JC
Burk
David H
DH
Smith
Steven R
SR
D000005:Abdomen / Q000033:anatomy & histology; D015502:Absorptiometry, Photon / Q000379:methods; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000378:metabolism*; D001794:Blood Pressure; D001823:Body Composition; D001831:Body Temperature; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D000860:Hypoxia; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D009929:Organ Size; D050177:Overweight / Q000503:physiopathology; D010100:Oxygen; D010313:Partial Pressure; D018579:Patient Selection; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010100:Oxygen