title: Hypoxia and adipocyte physiology: implications for adipose tissue dysfunction in obesity.
abstract: Hypoxia develops in white adipose tissue in obese mice, resulting in changes in adipocyte function that may underpin the dysregulation that leads to obesity-associated disorders. Whether hypoxia occurs in adipose tissue in human obesity is unclear, with recent studies contradicting earlier reports that this was the case. Adipocytes, both murine and human, exhibit extensive functional changes in culture in response to hypoxia, which alters the expression of up to 1,300 genes. These include genes encoding key adipokines such as leptin, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2), which are upregulated, and adiponectin, which is downregulated. Hypoxia also inhibits the expression of genes linked to oxidative metabolism while stimulating the expression of genes associated with glycolysis. Glucose uptake and lactate release by adipocytes are both stimulated by hypoxia, and insulin sensitivity falls. Preadipocytes and macrophages in adipose tissue also respond to hypoxia. The hypoxia-signaling pathway may provide a new target for the treatment of obesity-associated disorders.
authors.affiliation: Obesity Biology Research Unit, Institute of Ageing and Chronic Diseases, University of Liverpool, Liverpool L69 3GA United Kingdom, and Clore Laboratory, University of Buckingham, Buckingham MK18 1EG, United Kingdom; email: p.trayhurn@liverpool.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D052437:Adipocytes, Brown / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D052438:Adipocytes, White / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis; D000818:Animals; D015687:Cell Hypoxia; D004734:Energy Metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009765:Obesity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D051793:Hypoxia-Inducible Factor 1
keywords: brown fat; inflammation; leptin; oxygen; vascularization; white fat