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Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2017 Mar 01; Vol. 127 (3), pp. 1019-1030. Date of Electronic Publication: 2017 Feb 13. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Adipose Tissue pathology
Animals
B-Lymphocyte Subsets pathology
Dietary Fats adverse effects
Dietary Fats pharmacology
Insulin Resistance genetics
Leukotriene B4 genetics
Macrophages immunology
Macrophages pathology
Mice
Mice, Knockout
Obesity chemically induced
Obesity genetics
Obesity immunology
Obesity pathology
Receptors, Leukotriene B4 genetics
Signal Transduction genetics
T-Lymphocytes immunology
T-Lymphocytes pathology
Adipose Tissue immunology
B-Lymphocyte Subsets immunology
Insulin Resistance immunology
Leukotriene B4 immunology
Receptors, Leukotriene B4 immunology
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 127
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 28192375
- Full Text :
- https://doi.org/10.1172/JCI90350