Hypoxia and Adipocyte Physiology: Implications for Adipose Tissue Dysfunction in Obesity
Abstract
Hypoxia develops in white adipose tissue in obese mice, resulting in changes in adipocyte function that may underpin the dysregulation that leads to obesity-associated disorders. Whether hypoxia occurs in adipose tissue in human obesity is unclear, with recent studies contradicting earlier reports that this was the case. Adipocytes, both murine and human, exhibit extensive functional changes in culture in response to hypoxia, which alters the expression of up to 1,300 genes. These include genes encoding key adipokines such as leptin, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2), which are upregulated, and adiponectin, which is downregulated. Hypoxia also inhibits the expression of genes linked to oxidative metabolism while stimulating the expression of genes associated with glycolysis. Glucose uptake and lactate release by adipocytes are both stimulated by hypoxia, and insulin sensitivity falls. Preadipocytes and macrophages in adipose tissue also respond to hypoxia. The hypoxia-signaling pathway may provide a new target for the treatment of obesity-associated disorders.
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Adipocytes release proinflammatory factors such as IL-6 and macrophage migration inhibitory factor.
“Adipocytes release proinflammatory factors such as IL-6 and macrophage migration inhibitory factor (12).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [12]
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Nutrition, Cancer and Personalized Medicine
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Ceylan, H. İ., Silva, A. F., Ramírez‐Campillo, R., & Murawska‐Ciałowicz, E. (2024) · Biology · doi:10.3390/biology13050323 · Cited by 23 · see citing works
Rodríguez-Ayala, E., Gallegos-Cabrales, E. C., González-López, L., Laviada‐Molina, H., Salinas-Osornio, R. A., Nava‐González, E. J., Leal‐Berumen, I., Escudero‐Lourdes, C., Escalante-Araiza, F., Buenfil-Rello, F. A., et al. (2020) · Adipocyte · doi:10.1080/21623945.2020.1743116 · Cited by 20 · see citing works
Gold nanoparticles and obese adipose tissue microenvironment in cancer treatment
Essa, N., O’Connell, F., Prina‐Mello, A., O'Sullivan, J. N., & Marcone, S. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.10.017 · Cited by 20 · see citing works
Obesity-induced neuronal senescence: Unraveling the pathophysiological links
Ghosh, P., Fontanella, R. A., Scisciola, L., Taktaz, F., Pesapane, A., Basilicata, M. G., Tortorella, G., Matacchione, G., Capuano, A., Vietri, M. T., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102533 · Cited by 21 · see citing works
Zhou, C., Huang, Y., Da, M., Jin, W., & Zhou, F. (2023) · Discover Oncology · doi:10.1007/s12672-023-00704-4 · Cited by 19 · see citing works
Santamarina, A. B., Mennitti, L. V., de Souza, E. A., Mesquita, L. M. D. S., Noronha, I. H., Vasconcelos, J. R., Prado, C. M., & Pisani, L. P. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.09.024 · Cited by 19 · see citing works
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Reducing VEGFB expression regulates the balance of glucose and lipid metabolism in mice via VEGFR1
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Delivery of miRNAs to the adipose organ for metabolic health
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Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension
Papathanasiou, A. E., Spyropoulos, F., Michael, Z., Joung, K. E., Briana, D. D., Malamitsi‐Puchner, A., Mantzoros, C. S., & Christou, H. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031435 · Cited by 17 · see citing works
LACTATE CAN BE A MARKER OF METABOLIC SYNDROME IN SEVERE OBESITY?
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Regulation of adipogenesis by ceramide 1-phosphate
Ordoñez, M., Presa, N., Dominguez-Herrera, A., Trueba, M., & Gómez‐Muñoz, A. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.09.021 · Cited by 17 · see citing works
- Authors
- Trayhurn, P.
- Affiliations
- University of Liverpool (GB)
- Corresponding author
- Trayhurn, Paul
- ORCID
- Trayhurn, Paul
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2014-07-17
- Volume
- 34
- Issue
- 1
- Pages
- 207-236
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2112850039
- Cited by
- 194
- References
- 207
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 18 · 2021: 22 · 2020: 13 · 2019: 19 · 2018: 20 · 2017: 24 · 2016: 18 · 2015: 17 · 2014: 6
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- hypoxia, adipocytes, white adipose tissue, obesity, adipose tissue dysfunction, adipokines, leptin, adiponectin, interleukin-6, vascular endothelial growth factor, MMP-2, oxidative metabolism, glycolysis, glucose uptake, lactate release, insulin sensitivity, preadipocytes, macrophages, hypoxia signaling
- MeSH terms
- Animals, Energy Metabolism, Humans, Insulin Resistance, Macrophages, Models, Biological, Obesity, Cell Hypoxia, Adipogenesis, Hypoxia-Inducible Factor 1, Adipocytes, Brown, Adipocytes, White
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