Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity
- Blavatnik Institute, Harvard Medical School, United States
- Harvard T H Chan Bioinformatics Core, United States
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
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Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesityNCBI Gene Expression Omnibus, GSE147601.
Article and author information
Author details
Sudhir Gopal Tattikota
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
- Tania Reis, Univ Colorado, Denver, United States
Version history
- Received: April 6, 2020
- Accepted: October 26, 2020
- Accepted Manuscript published: October 27, 2020 (version 1)
- Version of Record published: December 21, 2020 (version 2)
- 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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Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity
eLife 9:e56969.
https://doi.org/10.7554/eLife.56969
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