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Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape

Author

Listed:
  • Isabel Reinisch

    (Medical University of Graz
    Eidgenössische Technische Hochschule Zürich (ETH))

  • Helene Michenthaler

    (Medical University of Graz)

  • Alba Sulaj

    (German Center for Diabetes Research (DZD)
    Heidelberg University Hospital)

  • Elisabeth Moyschewitz

    (Medical University of Graz)

  • Jelena Krstic

    (Medical University of Graz)

  • Markus Galhuber

    (Medical University of Graz)

  • Ruonan Xu

    (Medical University of Graz)

  • Zina Riahi

    (Medical University of Graz)

  • Tongtong Wang

    (Eidgenössische Technische Hochschule Zürich (ETH))

  • Nemanja Vujic

    (Medical University of Graz)

  • Melina Amor

    (Medical University of Graz)

  • Riccardo Zenezini Chiozzi

    (Utrecht University)

  • Martin Wabitsch

    (University Medical Center Ulm)

  • Dagmar Kolb

    (Medical University of Graz
    Medical University of Graz)

  • Anastasia Georgiadi

    (German Center for Diabetes Research (DZD))

  • Lisa Glawitsch

    (Medical University of Graz)

  • Ellen Heitzer

    (Medical University of Graz)

  • Tim J. Schulz

    (German Institute of Human Nutrition
    German Center for Diabetes Research (DZD)
    Institute of Nutritional Science)

  • Michael Schupp

    (Humboldt-Universität zu Berlin)

  • Wenfei Sun

    (Stanford University)

  • Hua Dong

    (University of Stanford)

  • Adhideb Ghosh

    (Eidgenössische Technische Hochschule Zürich (ETH)
    Functional Genomics Center Zurich, Eidgenössische Technische Hochschule Zürich (ETH))

  • Anne Hoffmann

    (Helmholtz Institute for Metabolic Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig)

  • Dagmar Kratky

    (Medical University of Graz
    BioTechMed-Graz)

  • Laura C. Hinte

    (Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich)

  • Ferdinand von Meyenn

    (Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich)

  • Albert J. R. Heck

    (Utrecht University)

  • Matthias Blüher

    (University of Leipzig)

  • Stephan Herzig

    (German Center for Diabetes Research (DZD)
    Heidelberg University Hospital)

  • Christian Wolfrum

    (Eidgenössische Technische Hochschule Zürich (ETH))

  • Andreas Prokesch

    (Medical University of Graz
    BioTechMed-Graz)

Abstract

In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.

Suggested Citation

  • Isabel Reinisch & Helene Michenthaler & Alba Sulaj & Elisabeth Moyschewitz & Jelena Krstic & Markus Galhuber & Ruonan Xu & Zina Riahi & Tongtong Wang & Nemanja Vujic & Melina Amor & Riccardo Zenezini , 2024. "Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45724-y
    DOI: 10.1038/s41467-024-45724-y
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    References listed on IDEAS

    as
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