Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling

2017/02/12 by Wei Ying, Joshua Wollam, Jachelle M. Ofrecio +7 · 127 citations
Chemistry · Immunology and Microbiology · Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Adipose tissue #Adipose tissue macrophages #Adoptive cell transfer #Atherosclerosis and Cardiovascular Diseases #Biology #Chemistry #Chemokine #Endocrinology #Glucose homeostasis #Immune Cell Function and Interaction #Immune system #Immunology #Inflammation #Insulin #Insulin resistance #Internal medicine #Leukotriene B4 #Medicine #T cell

paper · pdf · doi:10.1172/jci90350

published in Journal of Clinical Investigation 127(3), 1019-1030 (American Society for Clinical Investigation)

openalex publication_date 2017/02/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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.

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