Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling in Drosophila larvae

EMBO Rep. 2024 Oct;25(10):4410-4432. doi: 10.1038/s44319-024-00241-3. Epub 2024 Sep 9.

Abstract

The fat body in Drosophila larvae functions as a reserve tissue and participates in the regulation of organismal growth and homeostasis through its endocrine activity. To better understand its role in growth coordination, we induced fat body atrophy by knocking down several key enzymes of the glycolytic pathway in adipose cells. Our results show that impairing the last steps of glycolysis leads to a drastic drop in adipose cell size and lipid droplet content, and downregulation of the mTOR pathway and REPTOR transcriptional activity. Strikingly, fat body atrophy results in the distant disorganization of body wall muscles and the release of muscle-specific proteins in the hemolymph. Furthermore, we showed that REPTOR activity is required for fat body atrophy downstream of glycolysis inhibition, and that the effect of fat body atrophy on muscles depends on the production of TNF-α/egr and of the insulin pathway inhibitor ImpL2.

Keywords: Drosophila; Adipose Tissue; Glycolysis; Inter-Organ Communication; Muscle Wasting.

MeSH terms

  • Animals
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Fat Body* / metabolism
  • Glycolysis*
  • Larva* / genetics
  • Larva* / metabolism
  • Muscles* / metabolism
  • Muscles* / pathology
  • Receptor Protein-Tyrosine Kinases
  • Signal Transduction*
  • TOR Serine-Threonine Kinases* / metabolism
  • Tumor Necrosis Factor-alpha* / genetics
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Drosophila Proteins
  • egr protein, Drosophila
  • Receptor Protein-Tyrosine Kinases
  • tor protein, Drosophila
  • TOR Serine-Threonine Kinases
  • Tumor Necrosis Factor-alpha
  • ImpL2 protein, Drosophila