Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes.
The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl(2), on the expression and secretion of inflammation-related adipokines was examined in human adipocytes. Hypoxia led to a rapid and substantial increase (greater than sevenfold by 4 h of exposure to 1% O(2)) in the hypoxia-sensitive transcription factor, HIF-1alpha, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O(2) or CoCl(2)) led to a reduction (up to threefold over 24 h) in adiponectin and haptoglobin mRNA levels; adiponectin secretion also decreased. No changes were observed in TNFalpha expression. In contrast, hypoxia resulted in substantial increases in FIAF/angiopoietin-like protein 4, IL-6, leptin, MIF, PAI-1 and vascular endothelial growth factor (VEGF) mRNA levels. The largest increases were with FIAF (maximum 210-fold), leptin (maximum 29-fold) and VEGF (maximum 23-fold); these were reversed on return to normoxia. The secretion of IL-6, leptin, MIF and VEGF from the adipocytes was also stimulated by exposure to 1% O(2). These results demonstrate that hypoxia induces extensive changes in human adipocytes in the expression and release of inflammation-related adipokines. Hypoxia may underlie the development of the inflammatory response in adipocytes, leading to obesity-associated diseases.
Wang
Bohan
B
Obesity Biology Unit (Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network), School of Clinical Sciences, University Clinical Departments, University of Liverpool, Liverpool, UK.
Wood
I Stuart
IS
Trayhurn
Paul
P
D017667:Adipocytes / Q000502:physiology*; D054392:Adipokines / Q000096:biosynthesis* / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C499918:ADIPOQ protein, human; C474772:ANGPTL4 protein, human; D054392:Adipokines; D052242:Adiponectin; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C508600:IL6 protein, human; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C495677:SLC2A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C018021:cobaltous chloride