Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice

Robert W. O'Rourke, Ashley E. White, Monja D. Metcalf, Brian R. Winters, Brian S. Diggs, Xinxia Zhu, Daniel L. Marks

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.

Original languageEnglish (US)
Pages (from-to)1152-1161
Number of pages10
JournalMetabolism: Clinical and Experimental
Issue number8
StatePublished - Aug 2012


  • ATM
  • Adipose tissue macrophage
  • CD
  • Cluster differentiation
  • HFD
  • High fat diet
  • IFN
  • Interferon-gamma
  • KO
  • Knockout
  • Quantitative real-time polymerase chain reaction
  • SAT
  • SVF
  • Stromovascular cell fraction
  • Subcutaneous adipose tissue
  • VAT
  • Visceral adipose tissue
  • WT
  • Wild-type

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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