Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes

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Abstract
OBJECTIVE: Adipocyte hypertrophy combined with hyperplasia, observed during the growth of adipose tissue in obesity, might promote the occurrence of hypoxic areas within the tissue. The aim of the present study is to assess the influence of hypoxia on the expression and secretion of adipocyte-derived proangiogenic factors. DESIGN AND METHODS: Differentiated 3T3-F442A adipocytes were submitted either to ambient hypoxia (5% O2) or to chemically induced hypoxia by treatments with cobalt chloride or desferrioxamine. The activities of the matrix metalloproteinases 2 and 9 (MMP-2 and -9) were determined by gelatin zymography. The expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 (HIF-1), leptin, MMP-2 and -9 were studied by the use of Western blotting and RT-PCR analyses. RESULTS: Low oxygen pressure exposure and hypoxia mimics treatments were associated with increased glucose consumption and release of lactate in differentiated 3T3-F442A adipocytes. They also led to an upregulation of the expression of leptin, VEGF and MMPs. An enhanced accumulation of HIF-1 protein was observed in the hypoxic adipocyte nuclei. CONCLUSION: Hypoxia, in adipocytes, markedly enhances the expression of leptin, VEGF and MMPs and stimulates the HIF-1 pathway. The present data demonstrate that hypoxic adipocytes express more proangiogenic factors and suggest that hypoxia, if occuring in adipose tissue, might be a modulator of the angiogenic process.