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 SunHua 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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number1391
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

Fingerprint

Dive into the research topics of 'Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape'. Together they form a unique fingerprint.

Cite this