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Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance

Author

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  • Elaine Xu

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Mafalda M. A. Pereira

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Ismene Karakasilioti

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Sebastian Theurich

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Mona Al-Maarri

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Gunter Rappl

    (University of Cologne)

  • Ari Waisman

    (Institute for Molecular Medicine, University of Medical Centre of the Johannes Gutenberg University of Mainz)

  • F. Thomas Wunderlich

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne)

  • Jens C. Brüning

    (Max Planck Institute for Metabolism Research
    Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital
    Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne
    National Center for Diabetes Research (DZD))

Abstract

Low-grade inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Interleukin-6 (IL-6) is a crucial regulator of T cells and is increased in obesity. Here we report that classical IL-6 signalling in T cells promotes inflammation and insulin resistance during the first 8 weeks on a high-fat diet (HFD), but becomes dispensable at later stages (after 16 weeks). Mice with T cell-specific deficiency of IL-6 receptor-α (IL-6RαT-KO) exposed to a HFD display improved glucose tolerance, insulin sensitivity and inflammation in liver and EWAT after 8 weeks. However, after 16 weeks, insulin resistance in IL-6RαT-KO epididymal white adipose tissue (EWAT) is comparable to that of controls, whereas the inflammatory profile is significantly worse. This coincided with a shift from classical T cell IL-6 signalling at 8 weeks, to enhanced IL-6 trans-signalling at 16 weeks. Collectively, our studies reveal that IL-6 action in T cells through classical IL-6 signalling promotes inflammation and insulin resistance early during obesity development, which can be compensated for by enhanced IL-6 trans-signalling at later stages.

Suggested Citation

  • Elaine Xu & Mafalda M. A. Pereira & Ismene Karakasilioti & Sebastian Theurich & Mona Al-Maarri & Gunter Rappl & Ari Waisman & F. Thomas Wunderlich & Jens C. Brüning, 2017. "Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14803
    DOI: 10.1038/ncomms14803
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