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

International Journal of Obesity volume 27, pages 1187–1195 (2003)Cite this article

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 α (HIF-1α), 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-1α 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.

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Acknowledgements

We thank Christine Arragon for excellent technical assistance and Dr Cecilia Holm (Department of Cell and Molecular Biology, Lund University, Sweden) for providing us polyclonal chicken antibody against the hormone-sensitive lipase (HSL).

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  1. Unité de recherche sur les obésités, Institut National de la Santé et de la Recherche Médicale (INSERM U586), Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul-Sabatier, Toulouse, France

    K Lolmède, V Durand de Saint Front, J Galitzky, M Lafontan & A Bouloumié

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  1. K Lolmède
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Correspondence to K Lolmède.

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Lolmède, K., Durand de Saint Front, V., Galitzky, J. et al. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes. Int J Obes 27, 1187–1195 (2003). https://doi.org/10.1038/sj.ijo.0802407

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