RRC ID 58242
Author Robles-Murguia M, Rao D, Finkelstein D, Xu B, Fan Y, Demontis F.
Title Muscle-derived Dpp regulates feeding initiation via endocrine modulation of brain dopamine biosynthesis.
Journal Genes Dev
Abstract In animals, the brain regulates feeding behavior in response to local energy demands of peripheral tissues, which secrete orexigenic and anorexigenic hormones. Although skeletal muscle is a key peripheral tissue, it remains unknown whether muscle-secreted hormones regulate feeding. In Drosophila, we found that decapentaplegic (dpp), the homolog of human bone morphogenetic proteins BMP2 and BMP4, is a muscle-secreted factor (a myokine) that is induced by nutrient sensing and that circulates and signals to the brain. Muscle-restricted dpp RNAi promotes foraging and feeding initiation, whereas dpp overexpression reduces it. This regulation of feeding by muscle-derived Dpp stems from modulation of brain tyrosine hydroxylase (TH) expression and dopamine biosynthesis. Consistently, Dpp receptor signaling in dopaminergic neurons regulates TH expression and feeding initiation via the downstream transcriptional repressor Schnurri. Moreover, pharmacologic modulation of TH activity rescues the changes in feeding initiation due to modulation of dpp expression in muscle. These findings indicate that muscle-to-brain endocrine signaling mediated by the myokine Dpp regulates feeding behavior.
Volume 34(1-2)
Pages 37-52
Published 2020-1-1
DOI 10.1101/gad.329110.119
PII gad.329110.119
PMID 31831628
PMC PMC6938663
MeSH Animals Brain / physiology DNA-Binding Proteins / metabolism Dopamine Agents / pharmacology Dopaminergic Neurons / drug effects Dopaminergic Neurons / physiology Drosophila / enzymology Drosophila / genetics* Drosophila / metabolism* Drosophila Proteins / metabolism* Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Feeding Behavior / physiology* Levodopa / pharmacology Monoiodotyrosine / pharmacology Signal Transduction Transcription Factors / metabolism Tyrosine 3-Monooxygenase / genetics Up-Regulation
IF 9.527
Times Cited 0
Drosophila 14026R-1