title: Hypoxia and adipose tissue function and dysfunction in obesity.
abstract: The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.
authors.affiliation: Obesity Biology Research Unit, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010100:Oxygen / Q000097:blood*; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D018836:Inflammation Mediators; D010100:Oxygen