RRC ID 62703
Author Ghosh AC, Tattikota SG, Liu Y, Comjean A, Hu Y, Barrera V, Ho Sui SJ, Perrimon N.
Title Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity.
Journal Elife
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.
Volume 9
Published 2020-10-27
DOI 10.7554/eLife.56969
PII 56969
PMID 33107824
PMC PMC7752135
Resource
Drosophila 7103R-2 2115R-1 8222R-2