Inhibition of inflammation and iNOS improves lymphatic function in obesity
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Although recent studies have shown that obesity decreases lymphatic function, the cellular mechanisms regulating this response remain unknown. In the current study, we show that obesity results in perilymphatic accumulation of inflammatory cells and that local inhibition of this response with topical tacrolimus, an inhibitor of T cell differentiation, increases lymphatic vessel density, decreases perilymphatic iNOS expression, increases lymphatic vessel pumping frequency, and restores lymphatic clearance of interstitial fluid to normal levels. Although treatment of obese mice with 1400W, a selective inhibitor of iNOS, also improved lymphatic collecting vessel contractile function, it did not completely reverse lymphatic defects. Mice deficient in CD4(+) cells fed a high fat diet also gained weight relative to controls but were protected from lymphatic dysfunction. Taken together, our findings suggest that obesity-mediated lymphatic dysfunction is regulated by perilymphatic accumulation of inflammatory cells and that T cell inflammatory responses are necessary to initiate this effect.
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Lymphatic contractile dysfunction occurs in animal models of ageing, obesity, TNFα overexpression, iNOS activation, increased prostanoid production, and metabolic syndrome.
“and lymphatic contractile dysfunction in animal models of ageing (18), obesity (134, 135), TNFα overexpression (58), inducible nitric oxide synthase (iNOS) activation (136), increased prostanoid production (45), and metabolic syndrome (137).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [135]
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- Authors
- Torrisi, J. S., Hespe, G. E., Cuzzone, D. A., Savetsky, I. L., Nitti, M. D., Gardenier, J. C., García Nores, G. D., Jowhar, D., Kataru, R. P., & Mehrara, B. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Mehrara, Babak J.
- Venue
- Scientific Reports
- Published
- 2016-01-22
- Volume
- 6
- Issue
- 1
- Pages
- 19817-19817
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4726274
- OpenAlex
- W2399450046
- Cited by
- 97
- References
- 57
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 15 · 2020: 12 · 2019: 9 · 2018: 3 · 2017: 5 · 2016: 4
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748, T32 CA009501, NIH/NCI Cancer Center Support grant P30CA008748, Support Grant P30 CA008748)
- National Institutes of Health (NIH T32, NIH-R01, CA008748, NIH/NCI Cancer Center Support Grant P30 CA008748)
- National Heart, Lung, and Blood Institute (R01HL111130)
- National Cancer Institute (Grant P30-CA008748, CA008748, NIH/NCI Cancer Center Support Grant P30 CA008748., T32CA009685, Support Grant P30 CA008748, P30CA008748, T32CA009501)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity, lymphatic dysfunction, inflammation, inducible nitric oxide synthase, tacrolimus, 1400W, T cell differentiation, CD4+ T cells, lymphatic vessel density, lymphatic clearance, interstitial fluid, high-fat diet
- MeSH terms
- Administration, Topical, Animals, Biological Transport, Cell Movement, Dendritic Cells, Feeding Behavior, Inflammation, Lymph Nodes, Mice, Inbred C57BL, Mice, Obese, Obesity, Tacrolimus, Mice, Knockout, Lymphatic Vessels, Nitric Oxide Synthase Type II, Diet, High-Fat
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