Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation

Zheng Yin, Tuo Deng, Leif E. Peterson, Richeng Yu, Jianxin Lin, Dale J. Hamilton, Patrick R. Reardon, Vadim Sherman, Glenn Winnier, Ming Zhan, Christopher J. Lyon, Stephen T.C. Wong, Willa A. Hsueh

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Adipose tissue inflammation increases with obesity, but adipocyte vs. immune cell contributions are unclear. In the present study, transcriptome analyses were performed on highly-purified subcutaneous adipocytes from lean and obese women, and differentially expressed genes/pathways were determined in both adipocyte and stromal vascular fraction (SVF) samples. Adipocyte but not SVF expression of NOD-like receptor pathway genes, including NLRP3 and PYCARD, which regulate caspase-1-mediated IL-1β secretion, correlated with adiposity phenotypes and adipocyte class II major histocompatibility complex (MHCII) gene expression, but only MHCII remained after adjusting for age and body mass index. IFNγ stimulated adipocyte MHCII, NLRP3 and caspase-1 expression, while adipocyte MHCII-mediated CD4+ T cell activation, an important factor in adipose inflammation, induced IFNγ-dependent adipocyte IL-1β secretion. These results uncover a dialogue regulated by interactions among T cell IFNγ and adipocyte MHCII and NLRP3 inflammasome activity that appears to initiate and escalate adipose tissue inflammation during obesity.

Original languageEnglish (US)
Pages (from-to)80-87
Number of pages8
JournalMolecular and cellular endocrinology
Volume394
Issue number1-2
DOIs
StatePublished - Aug 25 2014

Keywords

  • Adipocyte
  • Inflammasome
  • Network modeling
  • NOD-like receptor pathway
  • Obesity
  • Transcriptome analysis

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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