Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes
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% O(2)) 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 alpha (HIF-1alpha), 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-1alpha 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 occurring in adipose tissue, might be a modulator of the angiogenic process.
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Several important hypoxia-associated genes, such as leptin and VEGF, are directly regulated by HIF-1.
“Several important hypoxia-associated genes, such as leptin and VEGF, are directly regulated by HIF-1 (25).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [25]
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- Authors
- Lolmède, K., Durand de Saint Front, V, Galitzky, J., Lafontan, M., & Bouloumié, A.
- Affiliations
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Lolmède, K
- Venue
- International Journal of Obesity
- Published
- 2003-09-26
- Volume
- 27
- Issue
- 10
- Pages
- 1187-1195
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2091725413
- Cited by
- 224
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 8 · 2015: 12 · 2014: 11 · 2013: 15 · 2012: 16
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- hypoxia, adipocytes, angiogenic factors, angiogenesis, leptin, vascular endothelial growth factor, hypoxia-inducible factor-1α, MMP-2, MMP-9, cobalt chloride, deferoxamine, glucose utilization, lactate release, adipose tissue, obesity
- MeSH terms
- Animals, Cell Differentiation, Glucose, Lactates, Oxygen, RNA, Messenger, Transcription Factors, Blotting, Western, Cell Hypoxia, Up-Regulation, 3T3 Cells, Adipocytes, Leptin, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Vascular Endothelial Growth Factor A, Angiogenic Proteins, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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