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

doi:10.1172/JCI90350

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

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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 language	English (US)
Pages (from-to)	1019-1030
Number of pages	12
Journal	Journal of Clinical Investigation
Volume	127
Issue number	3
DOIs	https://doi.org/10.1172/JCI90350
State	Published - Mar 1 2017

ASJC Scopus subject areas

General Medicine

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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.",

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

note = "Funding Information: Acknowledgments This study was funded by the American Heart Association (16POST31350039 to WY) and the US National Institute of Diabetes and Digestive and Kidney Diseases (DK033651, DK074868, DK063491, DK09062 to JM Olefsky).",

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T1 - Adipose tissue B2 cells promote insulin resistance through leukotriene LTB4/LTB4R1 signaling

AU - Ying, Wei

AU - Wollam, Joshua

AU - Ofrecio, Jachelle M.

AU - Bandyopadhyay, Gautam

AU - El Ouarrat, Dalila

AU - Lee, Yun Sok

AU - Oh, Dayoung

AU - Li, Pingping

AU - Osborn, Olivia

AU - Olefsky, Jerrold M.

N1 - Funding Information: Acknowledgments This study was funded by the American Heart Association (16POST31350039 to WY) and the US National Institute of Diabetes and Digestive and Kidney Diseases (DK033651, DK074868, DK063491, DK09062 to JM Olefsky).

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

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

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