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Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling
Open accessAbstract
Tissue inflammation is a key component of obesity-induced insulin resistance, with a variety of immune cell types accumulating in adipose tissue. Here, we have demonstrated increased numbers of B2 lymphocytes in obese adipose tissue and have shown that high-fat diet-induced (HFD-induced) insulin resistance is mitigated in B cell-deficient (Bnull) mice. Adoptive transfer of adipose tissue B2 cells (ATB2) from wild-type HFD donor mice into HFD Bnull recipients completely restored the effect of HFD to induce insulin resistance. Recruitment and activation of ATB2 cells was mediated by signaling through the chemokine leukotriene B4 (LTB4) and its receptor LTB4R1. Furthermore, the adverse effects of ATB2 cells on glucose homeostasis were partially dependent upon T cells and macrophages. These results demonstrate the importance of ATB2 cells in obesity-induced insulin resistance and suggest that inhibition of the LTB4/LTB4R1 axis might be a useful approach for developing insulin-sensitizing therapeutics.
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“Although the mechanisms underlying the expansion or infiltration of B cells into obese adipose tissue are poorly defined, signaling through the chemokine, leukotriene B4, and its receptor is required.( 46 )”
From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [46]
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“B2 cells accumulate in the obese adipose tissue where they contribute to local and systemic IR through pathogenic IgG antibodies( 45 ) and activation of T cells and macrophages.( 46 )”
From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [46]
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Metadata
- Authors
- Ying, W., Wollam, J., Ofrecio, J. M., Bandyopadhyay, G., El Ouarrat, D., Lee, Y. S., Oh, D. Y., Li, P., Osborn, O., & Olefsky, J. M.
- Affiliations
- Tongji University (CN)
- University of California San Diego (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Olefsky, Jerrold M.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2017-02-13
- Volume
- 127
- Issue
- 3
- Pages
- 1019-1030
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5330737
- OpenAlex
- W2587579012
- Cited by
- 128
- References
- 52
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 24 · 2020: 18 · 2019: 7 · 2018: 15 · 2017: 13
- FWCI
- 11.36
- 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)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Heart Association (16POST31350039)
- University of California, San Diego (DK063491)
- National Institute of Allergy and Infectious Diseases (P30AI036214)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK 074868, DK 033651, R37DK033651, R01DK101395, DK 09062, P01DK074868, F32DK009062, R01DK033651, P30DK063491)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- insulin resistance, obesity, leukotriene B4, high-fat diet, tissue inflammation, chemokine signaling, glucose homeostasis, T cells, macrophages, adoptive transfer, B cell-deficient mice
- MeSH terms
- Adipose Tissue, Animals, Dietary Fats, Insulin Resistance, Leukotriene B4, Macrophages, Obesity, T-Lymphocytes, Signal Transduction, B-Lymphocyte Subsets, Receptors, Leukotriene B4, Mice, Knockout, Mice
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