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Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease

Author

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  • Jörn F. Ziegler

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Chotima Böttcher

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Laboratory of Molecular Psychiatry and Department of Neuropsychiatry)

  • Marilena Letizia

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Cansu Yerinde

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Hao Wu

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Inka Freise

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Yasmina Rodriguez-Sillke

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Ani K. Stoyanova

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Martin E. Kreis

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Patrick Asbach

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Desiree Kunkel

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Berlin Institute of Health)

  • Josef Priller

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Laboratory of Molecular Psychiatry and Department of Neuropsychiatry
    BIH Berlin, DZNE Berlin and University of Edinburgh and UK DRI)

  • Ioannis Anagnostopoulos

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Charité Mitte)

  • Anja A. Kühl

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Core Facility of the Charité)

  • Konstanze Miehle

    (University of Leipzig Medical Center)

  • Michael Stumvoll

    (University of Leipzig Medical Center)

  • Florian Tran

    (Christian-Albrechts-University of Kiel)

  • Broder Fredrich

    (Christian-Albrechts-University of Kiel)

  • Michael Forster

    (Christian-Albrechts-University of Kiel)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Christian Bojarski

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Rainer Glauben

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Britt-Sabina Löscher

    (Christian-Albrechts-University of Kiel)

  • Britta Siegmund

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin)

  • Carl Weidinger

    (Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health
    Campus Benjamin Franklin
    Berlin Institute of Health)

Abstract

Leptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn’s disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn’s disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn’s disease patients regarding immune cell composition, function and metabolism and the effects of recombinant N-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn’s disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner.

Suggested Citation

  • Jörn F. Ziegler & Chotima Böttcher & Marilena Letizia & Cansu Yerinde & Hao Wu & Inka Freise & Yasmina Rodriguez-Sillke & Ani K. Stoyanova & Martin E. Kreis & Patrick Asbach & Desiree Kunkel & Josef P, 2019. "Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13559-7
    DOI: 10.1038/s41467-019-13559-7
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