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.
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
Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesityNCBI Gene Expression Omnibus, GSE147601.
- Arpan C Ghosh
- Norbert Perrimon
- Norbert Perrimon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Tania Reis, Univ Colorado, Denver, United States
© 2020, Ghosh et al.
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