Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels
Open accessAbstract
OBJECTIVE—The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis. RESEARCH DESIGN AND METHODS—We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice. RESULTS—We found that adipocyte differentiation takes place within cell clusters (which we designated adipogenic/angiogenic cell clusters) that contain multiple cell types, including endothelial cells and stromal cells that express CD34 and CD68 and bind lectin. There were close spatial and temporal interrelationships between blood vessel formation and adipogenesis, and the sprouting of new blood vessels from preexisting vasculature was coupled to adipocyte differentiation. CD34+ CD68+ lectin-binding cells could clearly be distinguished from CD34− CD68+ macrophages, which were scattered in the stroma and did not bind lectin. Adipogenic/angiogenic cell clusters can morphologically and immunohistochemically be distinguished from crown-like structures frequently seen in the late stages of adipose tissue obesity. Administration of anti–vascular endothelial growth factor (VEGF) antibodies inhibited not only angiogenesis but also the formation of adipogenic/angiogenic cell clusters, indicating that the coupling of adipogenesis and angiogenesis is essential for differentiation of adipocytes in obesity and that VEGF is a key mediator of that process. CONCLUSIONS—Living tissue imaging techniques provide novel evidence of the dynamic interactions between differentiating adipocytes, stromal cells, and angiogenesis in living obese adipose tissue.
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Macrophages aggregate, forming crown-like structures surrounding necrotic adipocytes in advanced obesity.
“Indeed, macrophages have been shown to aggregate, forming crown-like structures (CLSs) surrounding necrotic adipocytes in advanced obesity (10)(11)(12)(13).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [11]
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- Authors
- Nishimura, S., Manabe, I., Nagasaki, M., Hosoya, Y., Yamashita, H., Fujita, H., Ohsugi, M., Tobe, K., Kadowaki, T., Nagai, R., & Sugiura, S.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-06-01
- Volume
- 56
- Issue
- 6
- Pages
- 1517-1526
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2139716106
- Cited by
- 440
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 25 · 2020: 21 · 2019: 17 · 2018: 21 · 2017: 34 · 2016: 21 · 2015: 32 · 2014: 41 · 2013: 42 · 2012: 27
- FWCI
- 18.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- National Institute of Biomedical Innovation
- Japan Diabetes Foundation
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- 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
- adipogenesis, obesity, angiogenesis, adipose tissue, stromal cells, adipose tissue macrophages, vascular endothelial growth factor, db/db mice, crown-like structures, endothelial cells
- MeSH terms
- Adipose Tissue, Animals, Blood Vessels, Cell Differentiation, Endothelium, Vascular, Epididymis, Immunohistochemistry, Male, Mice, Inbred Strains, Obesity, Stromal Cells, Adipocytes, Microscopy, Confocal, Neovascularization, Physiologic, Models, Animal, Mice
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