Endocrinology

Pflügers Archiv - European Journal of Physiology

, Volume 455, Issue 3, pp 479-492

Open Access This content is freely available online to anyone, anywhere at any time.

Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes

  • Bohan WangAffiliated withObesity Biology Unit (Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network), School of Clinical Sciences, University Clinical Departments, University of Liverpool
  • , I. Stuart WoodAffiliated withObesity Biology Unit (Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network), School of Clinical Sciences, University Clinical Departments, University of Liverpool
  • , Paul TrayhurnAffiliated withObesity Biology Unit (Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network), School of Clinical Sciences, University Clinical Departments, University of Liverpool Email author 

Abstract

The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl2, 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% O2) in the hypoxia-sensitive transcription factor, HIF-1α, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O2 or CoCl2) 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 TNFα 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% O2. 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.

Keywords

Adipokines Adipose tissue Hypoxia Inflammation Obesity Metabolic syndrome