Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation

Tuo Deng; Christopher J. Lyon; Laurie J. Minze; Jianxin Lin; Jia Zou; Joey Z. Liu; Yuelan Ren; Zheng Yin; Dale J. Hamilton; Patrick R. Reardon; Vadim Sherman; Helen Y. Wang; Kevin J. Phillips; Paul Webb; Stephen T.C. Wong; Rong Fu Wang; Willa A. Hsueh

doi:10.1016/j.cmet.2013.02.009

Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation

Tuo Deng, Christopher J. Lyon, Laurie J. Minze, Jianxin Lin, Jia Zou, Joey Z. Liu, Yuelan Ren, Zheng Yin, Dale J. Hamilton, Patrick R. Reardon, Vadim Sherman, Helen Y. Wang, Kevin J. Phillips, Paul Webb, Stephen T.C. Wong, Rong Fu Wang, Willa A. Hsueh

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Abstract

Adipose-resident T cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex (MHCII) as an important component of high-fat-diet (HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2 weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII^-/- mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.

Original language	English (US)
Pages (from-to)	411-422
Number of pages	12
Journal	Cell Metabolism
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2013.02.009
State	Published - Mar 5 2013

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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Deng, T., Lyon, C. J., Minze, L. J., Lin, J., Zou, J., Liu, J. Z., Ren, Y., Yin, Z., Hamilton, D. J., Reardon, P. R., Sherman, V., Wang, H. Y., Phillips, K. J., Webb, P., Wong, S. T. C., Wang, R. F., & Hsueh, W. A. (2013). Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation. Cell Metabolism, 17(3), 411-422. https://doi.org/10.1016/j.cmet.2013.02.009

Deng, T, Lyon, CJ, Minze, LJ, Lin, J, Zou, J, Liu, JZ, Ren, Y, Yin, Z , Hamilton, DJ , Reardon, PR , Sherman, V, Wang, HY, Phillips, KJ, Webb, P, Wong, STC , Wang, RF & Hsueh, WA 2013, 'Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation', Cell Metabolism, vol. 17, no. 3, pp. 411-422. https://doi.org/10.1016/j.cmet.2013.02.009

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title = "Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation",

abstract = "Adipose-resident T cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex (MHCII) as an important component of high-fat-diet (HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2 weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII-/- mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.",

author = "Tuo Deng and Lyon, {Christopher J.} and Minze, {Laurie J.} and Jianxin Lin and Jia Zou and Liu, {Joey Z.} and Yuelan Ren and Zheng Yin and Hamilton, {Dale J.} and Reardon, {Patrick R.} and Vadim Sherman and Wang, {Helen Y.} and Phillips, {Kevin J.} and Paul Webb and Wong, {Stephen T.C.} and Wang, {Rong Fu} and Hsueh, {Willa A.}",

note = "Funding Information: This paper is dedicated to the late John Baxter for his enduring friendship and support. We thank Keyun Chen and Dr. Qiang Tong (Baylor College of Medicine) for assistance with the glucose uptake experiment. This work was supported by a generous grant from the MacDonald Foundation, a gift from the Zucker Family, and NIH grant R24DK087723 to W.A.H.; NIH grants R01CA121225 and U54CA149196 to S.T.C.W.; NIH grants R01CA101795, R01CA116408, and R01CA121191 to R.-f.W.; and ADA fellowship ADA 7-07-CVD-12 to T.D. ",

year = "2013",

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doi = "10.1016/j.cmet.2013.02.009",

language = "English (US)",

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T1 - Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation

AU - Deng, Tuo

AU - Lyon, Christopher J.

AU - Minze, Laurie J.

AU - Lin, Jianxin

AU - Zou, Jia

AU - Liu, Joey Z.

AU - Ren, Yuelan

AU - Yin, Zheng

AU - Hamilton, Dale J.

AU - Reardon, Patrick R.

AU - Sherman, Vadim

AU - Wang, Helen Y.

AU - Phillips, Kevin J.

AU - Webb, Paul

AU - Wong, Stephen T.C.

AU - Wang, Rong Fu

AU - Hsueh, Willa A.

N1 - Funding Information: This paper is dedicated to the late John Baxter for his enduring friendship and support. We thank Keyun Chen and Dr. Qiang Tong (Baylor College of Medicine) for assistance with the glucose uptake experiment. This work was supported by a generous grant from the MacDonald Foundation, a gift from the Zucker Family, and NIH grant R24DK087723 to W.A.H.; NIH grants R01CA121225 and U54CA149196 to S.T.C.W.; NIH grants R01CA101795, R01CA116408, and R01CA121191 to R.-f.W.; and ADA fellowship ADA 7-07-CVD-12 to T.D.

PY - 2013/3/5

Y1 - 2013/3/5

N2 - Adipose-resident T cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex (MHCII) as an important component of high-fat-diet (HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2 weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII-/- mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.

AB - Adipose-resident T cells (ARTs) regulate metabolic and inflammatory responses in obesity, but ART activation signals are poorly understood. Here, we describe class II major histocompatibility complex (MHCII) as an important component of high-fat-diet (HFD)-induced obesity. Microarray analysis of primary adipocytes revealed that multiple genes involved in MHCII antigen processing and presentation increased in obese women. In mice, adipocyte MHCII increased within 2 weeks on HFD, paralleling increases in proinflammatory ART markers and decreases in anti-inflammatory ART markers, and preceding adipose tissue macrophage (ATM) accumulation and proinflammatory M1 polarization. Mouse 3T3-L1 and primary adipocytes activated T cells in an antigen-specific, contact-dependent manner, indicating that adipocyte MHCII is functional. HFD-fed MHCII-/- mice developed less adipose inflammation and insulin resistance than did wild-type mice, despite developing similar adiposity. These investigations uncover a mechanism whereby a HFD-induced adipocyte/ART dialog involving MHCII instigates adipose inflammation and, together with ATM MHCII, escalates its progression.

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EP - 422

JO - Cell Metabolism

JF - Cell Metabolism

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ER -

Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation

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