Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue

R. W. O'Rourke, M. D. Metcalf, A. E. White, A. Madala, B. R. Winters, I. I. Maizlin, B. A. Jobe, C. T. Roberts, M. K. Slifka, D. L. Marks

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Background:Adipose tissue is a primary in vivo site of inflammation in obesity. Excess visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), imparts an increased risk of obesity-related comorbidities and mortality, and exhibits differences in inflammation. Defining depot-specific differences in inflammatory function may reveal underlying mechanisms of adipose-tissue-based inflammation.Methods:Stromovascular cell fractions (SVFs) from VAT and SAT from obese humans undergoing bariatric surgery were studied in an in vitro culture system with transcriptional profiling, flow cytometric phenotyping, enzyme-linked immunosorbent assay and intracellular cytokine staining.Results:Transcriptional profiling of SVF revealed differences in inflammatory transcript levels in VAT relative to SAT, including elevated interferon-γ (IFN-γ) transcript levels. VAT demonstrated a broad leukocytosis relative to SAT that included macrophages, T cells and natural killer (NK) cells. IFN-γ induced a proinflammatory cytokine expression pattern in SVF and adipose tissue macrophages (ATM). NK cells, which constitutively expressed IFN-γ, were present at higher frequency in VAT relative to SAT. Both T and NK cells from SVF expressed IFN-γ on activation, which was associated with tumor necrosis factor-α expression in macrophages.Conclusion:These data suggest involvement of NK cells and IFN-γ in regulating ATM phenotype and function in human obesity and a potential mechanism for the adverse physiologic effects of VAT.

Original languageEnglish (US)
Pages (from-to)978-990
Number of pages13
JournalInternational Journal of Obesity
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2009

Keywords

  • Adipose tissue
  • IFN-γ
  • Inflammation
  • NK cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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