Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 368, Issue 1, Pages 88-93Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.01.036
Keywords
adipocyte; adipokme; adipose tissue; HIF-1; gene expression; hypoxia; metallothionein; obesity; oxygen tension; PCR arrays
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C006364/1] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/C006364/1] Funding Source: Medline
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Hypoxia-signalling pathway PCR arrays were used to examine the integrated response of human adipocytes to low O-2 tension. Incubation of adipocytes in 1% O-2 for 24 h resulted in no change in the expression of 63 of the 84 genes on the arrays, a reduction in expression of 9 genes (including uncoupling protein 2) and increased expression of 12 genes. Substantial increases (>10-fold) in leptin, angiopoietin-like protein 4, VEGF and GLUT-I mRNA levels were observed. The expression of one gene, metallothionein-3 (MT-3), was dramatically (>600-fold) and rapidly (by 60 min) increased by hypoxia. MT-3 gene expression was also substantially induced by hypoxia mimetics (CoCl2, desferioxamine, dimethyloxalylglycine), indicating transcriptional regulation through HIF-1. Hypoxia additionally induced MT-3 expression in preadipocytes, and MT-3 mRNA was detected in human (obese) subcutaneous and omental adipose tissue. MT-3 is a highly hypoxia-inducible gene in human adipocytes; the protein may protect adipocytes from hypoxic damage. (C) 2008 Elsevier Inc. All rights reserved.
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