Metabolic Signatures of Human Adipose Tissue Hypoxia in Obesity

Abstract

Adipose tissue (AT) hypoxia has been proposed as the cause of obesity-related AT dysfunction, moving the tissue toward a proinflammatory phenotype. In humans, AT oxygenation has been assessed by expression of hypoxia-sensitive genes or direct assessment of O2 tension; the obvious read out of hypoxia, effects on intermediary metabolism, has not been investigated. We used tissue-specific venous catheterization of subcutaneous abdominal AT in humans to investigate oxygen-related metabolic processes, searching for metabolic signatures relating to hypoxia in obesity. O2 delivery to AT was reduced in obesity (P < 0.05). However, O2 consumption was low (<30% of resting forearm skeletal muscle [SM], P < 0.001); this was not related to obesity. AT primarily oxidized glucose, as demonstrated by a respiratory quotient close to 1.0 (higher than SM, P < 0.05). AT was a net producer of lactate, but there was an inverse relationship in venous outflow between lactate-to-pyruvate ratio (a marker of cytosolic redox state) and BMI, suggesting that AT is glycolytic but obese AT is not hypoxic. Although delivery of O2 to the obese AT is reduced, O2 consumption is low, and metabolic signatures of human AT do not support the notion of a hypoxic state in obesity.