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

Isabel Reinisch, Helene Michenthaler, Alba Sulaj, Elisabeth Moyschewitz, Jelena Krstic, Markus Galhuber, Ruonan Xu, Zina Riahi, Tongtong Wang, Nemanja Vujic, Melina Amor, Riccardo Zenezini Chiozzi, Martin Wabitsch, Dagmar Kolb, Anastasia Georgiadi, Lisa Glawitsch, Ellen Heitzer, Tim J. Schulz, Michael Schupp, Wenfei Sun, Hua Dong, Adhideb Ghosh, Anne Hoffmann, Dagmar Kratky, Laura C. Hinte, Ferdinand von Meyenn, Albert J. R. Heck, Matthias Blüher, Stephan Herzig, Christian Wolfrum and Andreas Prokesch ()
Additional contact information
Isabel Reinisch: Medical University of Graz
Helene Michenthaler: Medical University of Graz
Alba Sulaj: German Center for Diabetes Research (DZD)
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
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
Michael Schupp: Humboldt-Universität zu Berlin
Wenfei Sun: Stanford University
Hua Dong: University of Stanford
Adhideb Ghosh: 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
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)
Christian Wolfrum: Eidgenössische Technische Hochschule Zürich (ETH)
Andreas Prokesch: Medical University of Graz

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45724-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45724-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45724-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().