title: 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.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. leanne.hodson@ocdem.ox.ac.uk
authors.forename: Leanne
authors.initials: L
authors.lastname: Hodson
authors.forename: Sandy M
authors.initials: SM
authors.lastname: Humphreys
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.forename: Keith N
authors.initials: KN
authors.lastname: Frayn
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015687:Cell Hypoxia; D005215:Fasting; D005260:Female; D005542:Forearm; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D050177:Overweight / Q000097:blood / Q000378:metabolism*; D010101:Oxygen Consumption; D019518:Postprandial Period; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism; D050151:Subcutaneous Fat / Q000098:blood supply / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose