Nature Communications (Feb 2024)
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,
- Andreas Prokesch
Affiliations
- Isabel Reinisch
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Helene Michenthaler
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Alba Sulaj
- Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD)
- Elisabeth Moyschewitz
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Jelena Krstic
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Markus Galhuber
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Ruonan Xu
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Zina Riahi
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Tongtong Wang
- Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH)
- Nemanja Vujic
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz
- Melina Amor
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz
- Riccardo Zenezini Chiozzi
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Martin Wabitsch
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm
- Dagmar Kolb
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- Anastasia Georgiadi
- Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD)
- Lisa Glawitsch
- Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz
- Ellen Heitzer
- Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz
- Tim J. Schulz
- Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition
- Michael Schupp
- Institute of Pharmacology, Max Rubner Center (MRC) for Cardiovascular Metabolic Renal Research, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin
- Wenfei Sun
- Department of Bioengineering, Stanford University
- Hua Dong
- Stem Cell Biology and Regenerative Medicine Institute, University of Stanford
- Adhideb Ghosh
- Institute of Food Nutrition and Health, Department of Health Sciences and Technology, 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
- Gottfried Schatz Research Center, Molecular Biology and Biochemistry, 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
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University
- Matthias Blüher
- Department of Medicine, University of Leipzig
- Stephan Herzig
- Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD)
- Christian Wolfrum
- Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH)
- Andreas Prokesch
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz
- DOI
- https://doi.org/10.1038/s41467-024-45724-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
