Differences in Upper and Lower Body Adipose Tissue Oxygen Tension Contribute to the Adipose Tissue Phenotype in Humans

Context and Objectives: Upper and lower body adipose tissue (AT) exhibits opposing associations with obesity-related cardiometabolic diseases. Recent studies have suggested that altered AT oxygen tension (pO(2)) may contribute to AT dysfunction. Here, we compared in vivo abdominal (ABD) and femoral (FEM) subcutaneous AT pO(2) in women who are overweight and have obesity, and investigated the effects of physiological AT pO(2) on human adipocyte function.

Design: ABD and FEM subcutaneous AT pO(2) and AT blood flow (ATBF) were assessed in eight [BMI (body mass index) 34.4 +/- 1.6 kg/m(2)] postmenopausal women who were overweight with obesity and impaired glucose metabolism. ABD and FEM AT biopsy specimens were collected to determine adipocyte morphology and AT gene expression. Moreover, the effects of prolonged exposure (14 days) to physiological AT pO(2) on adipokine expression/secretion, mitochondrial respiration, and glucose uptake were investigated in differentiated human multipotent adipose-derived stem cells.

Results: AT pO(2) was higher in ABD than FEM AT (62.7 +/- 6.6 vs 50.0 +/- 4.5 mm Hg, P = 0.013), whereas ATBF was comparable between depots. Maximal uncoupled oxygen consumption rates were substantially lower in ABD than FEM adipocytes for all pO(2) conditions. Low physiological pO(2) (5% O-2) decreased proinflammatory gene expression, increased basal glucose uptake, and altered adipokine secretion in ABD and FEM adipocytes.

Conclusions: We demonstrated for the first time, to our knowledge, that AT pO(2) is higher in ABD than FEM subcutaneous AT in women who are overweight/with obesity, partly due to a lower oxygen consumption rate in ABD adipocytes. Moreover, low physiological pO(2) decreased proinflammatory gene expression and improved the metabolic phenotype in differentiated human adipocytes, whereas more heterogeneous effects on adipokine secretion were found.