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

International Journal of Obesity volume 33, pages 978–990 (2009)Cite this article

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.

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Acknowledgements

This work was supported by an American Surgical Association Foundation Fellowship Award (RWO), National Institutes of Health grants K08 DK074397 (RWO), K23 DK066165 (BAJ), R03 CA105959 (BAJ), AI054458 (MKS), an Oregon National Primate Research Center grant RR00163 (MKS) as well as the Oregon Clinical and Translational Research Institute, grant numbers UL1 RR024140 and TL1 RR024159 from the National Center for Research Resources, a component of the National Institutes of Health, and National Institutes of Health Roadmap for Medical Research (BRW and RWO). We thank Ms Nichelle Tran for expert administrative and graphic design assistance.

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Authors and Affiliations

  1. Department of Surgery, Oregon Health and Science University, Portland, OR, USA

    R W O'Rourke, M D Metcalf, A E White & A Madala

  2. School of Medicine, Oregon Health and Science University, Portland, OR, USA

    B R Winters & I I Maizlin

  3. Division of Thoracic and Foregut Surgery, The Heart, Lung, and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    B A Jobe

  4. Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA

    C T Roberts Jr & D L Marks

  5. Oregon National Primate Research Center, Beaverton, OR, USA

    C T Roberts Jr

  6. Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR, USA

    M K Slifka

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O'Rourke, R., Metcalf, M., White, A. et al. Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-γ in inflammation in human adipose tissue. Int J Obes 33, 978–990 (2009). https://doi.org/10.1038/ijo.2009.133

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