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PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

Author

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  • G. I. Lancaster

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute)

  • H. L. Kammoun

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute)

  • M. J. Kraakman

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute)

  • G. M. Kowalski

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute
    School of Exercise and Nutritional Sciences, Deakin University)

  • C. R. Bruce

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute
    School of Exercise and Nutritional Sciences, Deakin University)

  • M. A. Febbraio

    (Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute
    Garvan Institute of Medical Research)

Abstract

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation.

Suggested Citation

  • G. I. Lancaster & H. L. Kammoun & M. J. Kraakman & G. M. Kowalski & C. R. Bruce & M. A. Febbraio, 2016. "PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10626
    DOI: 10.1038/ncomms10626
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