title: Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling.
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.
authors.forename: Wei
authors.initials: W
authors.lastname: Ying
authors.forename: Joshua
authors.initials: J
authors.lastname: Wollam
authors.forename: Jachelle M
authors.initials: JM
authors.lastname: Ofrecio
authors.forename: Gautam
authors.initials: G
authors.lastname: Bandyopadhyay
authors.forename: Dalila
authors.initials: D
authors.lastname: El Ouarrat
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Da Young
authors.initials: DY
authors.lastname: Oh
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.forename: Olivia
authors.initials: O
authors.lastname: Osborn
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000276:immunology*; D007975:Leukotriene B4 / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D004041:Dietary Fats; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4