E2F/Dp inactivation in fat body cells triggers systemic metabolic changes

  1. Maria Paula Zappia
  2. Ana Guarner
  3. Nadia Kellie-Smith
  4. Alice Rogers
  5. Robert Morris
  6. Brandon Nicolay
  7. Myriam Boukhali
  8. Wilhelm Haas
  9. Nicholas Dyson
  10. Maxim V Frolov  Is a corresponding author
  1. University of Illinois at Chicago, United States
  2. Massachusetts General Hospital, United States
  3. 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

The following data sets were generated

Article and author information

Author details

  1. Maria Paula Zappia

    Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ana Guarner

    Cancer Center, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nadia Kellie-Smith

    Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alice Rogers

    Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Morris

    Cancer Center, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Brandon Nicolay

    Cancer Center, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Myriam Boukhali

    Cancer Center, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Wilhelm Haas

    Massachusetts General Hospital CancerCenter and Harvard Medical School, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Nicholas Dyson

    Cancer Center, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Maxim V Frolov

    Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, United States
    For correspondence
    mfrolov@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3953-3739

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

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: February 22, 2021
  2. Preprint posted: April 9, 2021 (view preprint)
  3. Accepted: July 11, 2021
  4. Accepted Manuscript published: July 12, 2021 (version 1)
  5. 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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  1. Maria Paula Zappia
  2. Ana Guarner
  3. Nadia Kellie-Smith
  4. Alice Rogers
  5. Robert Morris
  6. Brandon Nicolay
  7. Myriam Boukhali
  8. Wilhelm Haas
  9. Nicholas Dyson
  10. Maxim V Frolov
(2021)
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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