E2F/Dp inactivation in fat body cells triggers systemic metabolic changes
- University of Illinois at Chicago, United States
- Massachusetts General Hospital, United States
- Massachusetts General Hospital CancerCenter and Harvard Medical School, United States
Abstract
The E2F transcription factors play a critical role in controlling cell fate. In Drosophila, the inactivation of E2F in either muscle or fat body results in lethality, suggesting an essential function for E2F in these tissues. However, the cellular and organismal consequences of inactivating E2F in these tissues are not fully understood. Here, we show that the E2F loss exerts both tissue-intrinsic and systemic effects. The proteomic profiling of E2F-deficient muscle and fat body revealed that E2F regulates carbohydrate metabolism, a conclusion further supported by metabolomic profiling. Intriguingly, animals with E2F-deficient fat body had a lower level of circulating trehalose and reduced storage of fat. Strikingly, a sugar supplement was sufficient to restore both trehalose and fat levels, and subsequently, rescued animal lethality. Collectively, our data highlight the unexpected complexity of E2F mutant phenotype, which is a result of combining both tissue-specific and systemic changes that contribute to animal development.
Data availability
All mass spectrometer RAW files for quantitative proteomics analysis can be accessed through the MassIVE data repository (massive.ucsd.edu) under the accession number MSV000086854
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The impact of E2F/Dp inactivation on metabolism differs between muscles and fat body cellsMassIVE data repository (massive.ucsd.edu),MSV000086854.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R35GM131707)
- Maxim V Frolov
National Institute of General Medical Sciences (R01GM117413)
- Nicholas Dyson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Publication history
- Received: February 22, 2021
- Preprint posted: April 9, 2021 (view preprint)
- Accepted: July 11, 2021
- Accepted Manuscript published: July 12, 2021 (version 1)
- Version of Record published: July 22, 2021 (version 2)
Copyright
© 2021, Zappia et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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E2F/Dp inactivation in fat body cells triggers systemic metabolic changes
eLife 10:e67753.
https://doi.org/10.7554/eLife.67753
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