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In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue
Open accessAbstract
To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell types, real-time, in vivo analysis is necessary. We developed a technique based on confocal laser microscopy that enabled us to analyze and compare the 3-dimensional structures, cellular dynamics, and vascular function within mouse lean and obese adipose tissue in vivo with high spatiotemporal resolution. We found increased leukocyte-EC-platelet interaction in the microcirculation of obese visceral adipose tissue in ob/ob and high-fat diet-induced obese mice. These changes were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Local platelet activation in obese adipose tissue was indicated by increased P-selectin expression and formation of monocyte-platelet conjugates. We observed upregulated expression of adhesion molecules on macrophages and ECs in obese visceral adipose tissue, suggesting that interactions between these cells contribute to local activation of inflammatory processes. Furthermore, administration of anti-ICAM-1 antibody normalized the cell dynamics seen in obese visceral fat. This imaging technique to analyze the complex cellular interplay within obese adipose tissue allowed us to show that visceral adipose tissue obesity is an inflammatory disease. In addition, this technique may prove to be a valuable tool to evaluate potential therapeutic interventions.
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“As in obese AT, tumor vasculature is significantly more permeable than that of normal tissue (87), a characteristic that promotes immune cell extravasation and fibrosis.”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [87]
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Metadata
- Authors
- Nishimura, S., Manabe, I., Nagasaki, M., Seo, K., Yamashita, H., Hosoya, Y., Ohsugi, M., Tobe, K., Kadowaki, T., Nagai, R., & Sugiura, S.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2008-01-17
- Volume
- 118
- Issue
- 2
- Pages
- 710-21
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2200301
- OpenAlex
- W2084622089
- Cited by
- 277
- References
- 56
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 11 · 2017: 14 · 2016: 22 · 2015: 26 · 2014: 23 · 2013: 26 · 2012: 24
- FWCI
- 16.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cell Science Research Foundation
- 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
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- obesity, visceral adipose tissue, inflammation, leukocyte-endothelium interaction, platelet activation, P-selectin, ICAM-1, leukocyte adhesion, macrophages, endothelial cells, in vivo confocal microscopy, high-fat diet-induced obesity, ob/ob mice
- MeSH terms
- Animals, Antibodies, Blood Platelets, Capillaries, Capillary Permeability, Endothelium, Vascular, Leukocytes, Macrophages, Mice, Obese, Microcirculation, Obesity, Panniculitis, Cell Adhesion Molecules, Microscopy, Confocal, Intercellular Adhesion Molecule-1, P-Selectin, Intra-Abdominal Fat, Mice
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