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The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance

Author

Listed:
  • Jérémie Gautheron

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

  • Mihael Vucur

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

  • Anne T. Schneider

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

  • Ilenia Severi

    (University of Ancona)

  • Christoph Roderburg

    (University Hospital RWTH Aachen)

  • Sanchari Roy

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

  • Matthias Bartneck

    (University Hospital RWTH Aachen)

  • Peter Schrammen

    (University Hospital RWTH Aachen)

  • Mauricio Berriel Diaz

    (Institute for Diabetes and Cancer IDC Helmholtz Center Munich, Neuherberg 85764 and Joint Heidelberg‐IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University)

  • Josef Ehling

    (University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen)

  • Felix Gremse

    (University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen)

  • Felix Heymann

    (University Hospital RWTH Aachen)

  • Christiane Koppe

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

  • Twan Lammers

    (University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen)

  • Fabian Kiessling

    (University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen)

  • Niels Van Best

    (Institut of Medical Microbiology, University Hospital RWTH Aachen)

  • Oliver Pabst

    (Institut of Medical Microbiology, University Hospital RWTH Aachen)

  • Gilles Courtois

    (Inserm U1038, BIG, CEA)

  • Andreas Linkermann

    (Christian‐Albrechts‐University)

  • Stefan Krautwald

    (Christian‐Albrechts‐University)

  • Ulf P. Neumann

    (University Hospital RWTH Aachen)

  • Frank Tacke

    (University Hospital RWTH Aachen)

  • Christian Trautwein

    (University Hospital RWTH Aachen)

  • Douglas R. Green

    (St Jude Children’s Research Hospital)

  • Thomas Longerich

    (Institute of Pathology, University Hospital RWTH Aachen)

  • Norbert Frey

    (University Hospital Schleswig-Holstein, Campus Kiel)

  • Mark Luedde

    (University Hospital Schleswig-Holstein, Campus Kiel)

  • Matthias Bluher

    (University of Leipzig)

  • Stephan Herzig

    (Institute for Diabetes and Cancer IDC Helmholtz Center Munich, Neuherberg 85764 and Joint Heidelberg‐IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University
    German Center for Diabetes Research (DZD))

  • Mathias Heikenwalder

    (German Cancer Research Center (DKFZ))

  • Tom Luedde

    (University Hospital RWTH Aachen
    University Hospital RWTH Aachen)

Abstract

Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients.

Suggested Citation

  • Jérémie Gautheron & Mihael Vucur & Anne T. Schneider & Ilenia Severi & Christoph Roderburg & Sanchari Roy & Matthias Bartneck & Peter Schrammen & Mauricio Berriel Diaz & Josef Ehling & Felix Gremse & , 2016. "The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance," Nature Communications, Nature, vol. 7(1), pages 1-16, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11869
    DOI: 10.1038/ncomms11869
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