1. Genetics and Genomics
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Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity

  1. Arpan C Ghosh  Is a corresponding author
  2. Sudhir Gopal Tattikota
  3. Yifang Liu
  4. Aram Comjean
  5. Yanhui Hu
  6. Victor Barrera
  7. Shannan J Ho Sui
  8. Norbert Perrimon  Is a corresponding author
  1. Blavatnik Institute, Harvard Medical School, United States
  2. Harvard T H Chan Bioinformatics Core, United States
Research Article
  • Cited 6
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Cite this article as: eLife 2020;9:e56969 doi: 10.7554/eLife.56969

Abstract

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.

Data availability

Sequencing data have been deposited in GEO under the accession number GSE147601. Elsewhere, data can be visualized at: www.flyrnai.org/scRNA/abdomen/. Data code can accessed at: https://github.com/liuyifang/Drosophila-PDGF-VEGF-signaling-from-muscles-to-hepatocyte-like-cells-protects-against-obesity

The following data sets were generated

Article and author information

Author details

  1. Arpan C Ghosh

    Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    For correspondence
    arpan_ghosh@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6553-938X
  2. Sudhir Gopal Tattikota

    Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0318-5533
  3. Yifang Liu

    Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Aram Comjean

    Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yanhui Hu

    Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Victor Barrera

    Biostatistics, Harvard T H Chan Bioinformatics Core, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0590-4634
  7. Shannan J Ho Sui

    Biostatistics, Harvard T H Chan Bioinformatics Core, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Norbert Perrimon

    Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States
    For correspondence
    perrimon@genetics.med.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

American Heart Association (18POST33990414)

  • Arpan C Ghosh

National Institute of Arthritis and Musculoskeletal and Skin Diseases (5RO1AR05735210)

  • Norbert Perrimon

National Institutes of Health (P01CA120964)

  • Norbert Perrimon

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tania Reis, Univ Colorado, Denver, United States

Publication history

  1. Received: April 6, 2020
  2. Accepted: October 26, 2020
  3. Accepted Manuscript published: October 27, 2020 (version 1)
  4. Version of Record published: December 21, 2020 (version 2)
  5. Version of Record updated: January 21, 2021 (version 3)

Copyright

© 2020, Ghosh 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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