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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0156v1 198/1/127    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, B. Articles by Trayhurn, P. PubMed PubMed Citation Articles by Wang, B. Articles by Trayhurn, P.

Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Duncan Building, Liverpool L69 3GA, UK

(Correspondence should be addressed to P Trayhurn; Email: p.trayhurn{at}liverpool.ac.uk)

The effect of hypoxia on the expression and secretion of major adipokines by human preadipocytes has been examined. Hypoxia (1% O₂) led to an increase in the HIF-1 transcription factor subunit in cultured preadipocytes, as did incubation with the hypoxia mimetic CoCl₂. Leptin mRNA was essentially undetectable in preadipocytes incubated under normoxia (21% O₂), but exposure to 1% O₂, or CoCl₂, for 4 or 24 h resulted in an induction of leptin gene expression (measured by real-time PCR). Immunoreactive leptin was not detected in the medium from normoxic preadipocytes, but was present in the medium from the hypoxic cells. Hypoxia stimulated expression of the GLUT-1 facilitative glucose transporter gene and the vascular endothelial growth factor (VEGF) gene in preadipocytes, as in adipocytes. PPAR and aP2 mRNA levels, markers of adipocyte differentiation, were reduced by hypoxia in both cell types. In marked contrast to adipocytes, interleukin-6 (IL-6), angiopoietin-like protein 4, and plasminogen activator inhibitor-1 expression by preadipocytes was not stimulated by low O₂ tension. Consistent with the gene expression results, VEGF release into the medium from preadipocytes was increased by hypoxia, but there was no change in IL-6 secretion. It is concluded that hypoxia induces human preadipocytes to synthesize and secrete leptin. Preadipocytes and adipocytes differ in their responsiveness to low O₂ tension, maturation of the response to hypoxia developing on differentiation.