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| Status |
Public on Jan 16, 2024 |
| Title |
Adipocyte p53 coordinates the adipose tissue immune cell landscape upon intermittent fasting |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.
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| Overall design |
organism: mus musculus, tissue type: epididymal adipose tissue, data type: single-nuclei RNA sequencing data, groups: high-fat diet ad libitum fed (HFD-AL), high-fat diet fed and intermittent fasted (HFD-IF), high-fat diet fed and intermittent fasted, adipocyte-specific p53 KO mice
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| Contributor(s) |
Reinisch I, Prokesch A |
| Citation(s) |
38360943 |
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| Submission date |
Apr 13, 2023 |
| Last update date |
Feb 26, 2024 |
| Contact name |
Genome Informatics |
| E-mail(s) |
fgcz.gi@gmail.com
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| Organization name |
ETH ZURICH / University of Zurich
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| Department |
Functional Genomics Center Zurich (FGCZ)
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| Street address |
Winterthurerstrasse 190
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| City |
Zurich |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA955294 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE229690_RAW.tar |
578.9 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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