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

Autor: Reinisch I; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.; Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), Schwerzenbach, Switzerland., Michenthaler H; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Sulaj A; Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD), Neuherberg, Germany.; Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany., Moyschewitz E; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Krstic J; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Galhuber M; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Xu R; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Riahi Z; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria., Wang T; Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), Schwerzenbach, Switzerland., Vujic N; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Amor M; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Zenezini Chiozzi R; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Wabitsch M; Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany., Kolb D; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.; Core Facility Ultrastructure Analysis, Medical University of Graz, Graz, Austria., Georgiadi A; Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD), Neuherberg, Germany., Glawitsch L; Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria., Heitzer E; Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria., Schulz TJ; Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition, Nuthetal, Germany.; German Center for Diabetes Research (DZD), München-Neuherberg, Germany.; University of Potsdam, Institute of Nutritional Science, Nuthetal, Germany., Schupp M; 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, Berlin, Germany., Sun W; Department of Bioengineering, Stanford University, Stanford, CA, USA., Dong H; Stem Cell Biology and Regenerative Medicine Institute, University of Stanford, Stanford, CA, USA., Ghosh A; Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), Schwerzenbach, Switzerland.; Functional Genomics Center Zurich, Eidgenössische Technische Hochschule Zürich (ETH), Zurich, Switzerland., Hoffmann A; Helmholtz Institute for Metabolic Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Kratky D; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Hinte LC; Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., von Meyenn F; Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Heck AJR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Blüher M; Department of Medicine, University of Leipzig, Leipzig, Germany., Herzig S; Institute for Diabetes and Cancer, Helmholtz Munich, German Center for Diabetes Research (DZD), Neuherberg, Germany.; Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany., Wolfrum C; Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zürich (ETH), Schwerzenbach, Switzerland., Prokesch A; Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria. andreas.prokesch@medunigraz.at.; BioTechMed-Graz, Graz, Austria. andreas.prokesch@medunigraz.at.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 15; Vol. 15 (1), pp. 1391. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1038/s41467-024-45724-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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