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

Research output: Contribution to journalArticle

184 Scopus citations

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 languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalCell Metabolism
Volume17
Issue number3
DOIs
StatePublished - Mar 5 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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