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

Wei Ying, Joshua Wollam, Jachelle M. Ofrecio, Gautam Bandyopadhyay, Dalila El Ouarrat, Yun Sok Lee, Dayoung Oh, Pingping Li, Olivia Osborn, Jerrold M. Olefsky

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1019-1030
Number of pages12
JournalJournal of Clinical Investigation
Volume127
Issue number3
DOIs
StatePublished - Mar 1 2017

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Leukotriene B4
Leukotrienes
Insulin Resistance
Adipose Tissue
Leukotriene B4 Receptors
Obesity
Adoptive Transfer
Lymphocyte Count
High Fat Diet
Chemokines
Homeostasis
B-Lymphocytes
Macrophages
Insulin
Inflammation
T-Lymphocytes
Glucose

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ying, W., Wollam, J., Ofrecio, J. M., Bandyopadhyay, G., El Ouarrat, D., Lee, Y. S., ... Olefsky, J. M. (2017). Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. Journal of Clinical Investigation, 127(3), 1019-1030. https://doi.org/10.1172/JCI90350

Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. / Ying, Wei; Wollam, Joshua; Ofrecio, Jachelle M.; Bandyopadhyay, Gautam; El Ouarrat, Dalila; Lee, Yun Sok; Oh, Dayoung; Li, Pingping; Osborn, Olivia; Olefsky, Jerrold M.

In: Journal of Clinical Investigation, Vol. 127, No. 3, 01.03.2017, p. 1019-1030.

Research output: Contribution to journalArticle

Ying, W, Wollam, J, Ofrecio, JM, Bandyopadhyay, G, El Ouarrat, D, Lee, YS, Oh, D, Li, P, Osborn, O & Olefsky, JM 2017, 'Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling', Journal of Clinical Investigation, vol. 127, no. 3, pp. 1019-1030. https://doi.org/10.1172/JCI90350
Ying W, Wollam J, Ofrecio JM, Bandyopadhyay G, El Ouarrat D, Lee YS et al. Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. Journal of Clinical Investigation. 2017 Mar 1;127(3):1019-1030. https://doi.org/10.1172/JCI90350
Ying, Wei ; Wollam, Joshua ; Ofrecio, Jachelle M. ; Bandyopadhyay, Gautam ; El Ouarrat, Dalila ; Lee, Yun Sok ; Oh, Dayoung ; Li, Pingping ; Osborn, Olivia ; Olefsky, Jerrold M. / Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling. In: Journal of Clinical Investigation. 2017 ; Vol. 127, No. 3. pp. 1019-1030.
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