title: Modulation of adipokine production, glucose uptake and lactate release in human adipocytes by small changes in oxygen tension.
abstract: Adipose tissue becomes hypoxic in obesity, and cell culture studies have demonstrated that hypoxia leads to major changes in adipocyte function. Studies on the response of adipocytes to low O₂ tension have employed marked hypoxia (1% O₂). Here, we have examined the effects of modest hypoxia, utilising differing concentrations of O₂ (1-21%), on adipokine production and glucose uptake by human adipocytes. Incubation with 10% O₂ (24 h) increased expression of the leptin, vascular endothelial growth factor (VEGF) and Angptl4 genes, while leptin expression was elevated even at 15% O₂ (compared to 'normoxia'-21% O₂). Overall, there was a concentration-dependent increase in the expression of these genes as O₂ fell, with the highest mRNA level evident at 1% O₂. Parallel changes were observed in the secretion of leptin, VEGF and IL-6 into the medium, an increased release being evident at 10% O₂ (15% O(2) for leptin). Adiponectin gene expression was reduced at 15% O₂ and below, while adiponectin release was significantly reduced at 5% O₂. Both 2-deoxy-D: -glucose uptake and lactate release showed progressive increases as O₂ concentration fell, being significantly raised at 10% and 5% O₂, respectively. The alterations in substrate transport were accompanied by parallel changes in transporter gene expression, GLUT1 and MCT1 mRNA level increasing from 15% and 10% O₂, respectively. These results indicate that marked responses to reduced O₂ concentration are exhibited by human adipocytes at O₂ levels well above those associated with hypoxia and employed in cell culture studies. Adipocytes are sensitive to small changes in O₂ tension.
authors.affiliation: Obesity Biology Research Unit, Institute of Ageing and Chronic Diseases, University of Liverpool, Duncan Building, Liverpool, UK.
authors.forename: I Stuart
authors.initials: IS
authors.lastname: Wood
authors.forename: Tanya
authors.initials: T
authors.lastname: Stezhka
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D054392:Adipokines / Q000096:biosynthesis*; D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D054392:Adipokines; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D050556:Fatty Acid-Binding Proteins; D005947:Glucose; D051272:Glucose Transporter Type 1; D015850:Interleukin-6; D019344:Lactic Acid; D020738:Leptin; D027501:Monocarboxylic Acid Transporters; D010100:Oxygen; D027981:Symporters; D042461:Vascular Endothelial Growth Factor A; D000099233:Monocarboxylate Transport Protein 1; C474772:ANGPTL4 protein, human; C493410:FABP4 protein, human; C495677:SLC2A1 protein, human