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

Pflugers Arch. 2007 Dec;455(3):479-92. doi: 10.1007/s00424-007-0301-8. Epub 2007 Jul 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology*
  • Adipokines / biosynthesis*
  • Adipokines / metabolism*
  • Adiponectin / metabolism
  • Adult
  • Angiopoietin-like 4 Protein
  • Angiopoietins / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cobalt / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 1 / biosynthesis*
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Interleukin-6 / metabolism
  • Intramolecular Oxidoreductases / metabolism
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • ADIPOQ protein, human
  • ANGPTL4 protein, human
  • Adipokines
  • Adiponectin
  • Angiopoietin-like 4 Protein
  • Angiopoietins
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IL6 protein, human
  • Interleukin-6
  • Macrophage Migration-Inhibitory Factors
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • SLC2A1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cobalt
  • Intramolecular Oxidoreductases
  • MIF protein, human
  • cobaltous chloride