fs(1)h controls metabolic and immune function and enhances survival via AKT and FOXO in Drosophila

Dis Model Mech. 2019 Apr 4;12(4):dmm037259. doi: 10.1242/dmm.037259.


The Drosophila fat body is the primary organ of energy storage as well as being responsible for the humoral response to infection. Its physiological function is of critical importance to the survival of the organism; however, many molecular regulators of its function remain ill-defined. Here, we show that the Drosophila melanogaster bromodomain-containing protein FS(1)H is required in the fat body for normal lifespan as well as metabolic and immune homeostasis. Flies lacking fat body fs(1)h exhibit short lifespan, increased expression of immune target genes, an inability to metabolize triglyceride, and low basal AKT activity, mostly resulting from systemic defects in insulin signalling. Removal of a single copy of the AKT-responsive transcription factor foxo normalises lifespan, metabolic function, uninduced immune gene expression and AKT activity. We suggest that the promotion of systemic insulin signalling activity is a key in vivo function of fat body fs(1)h This article has an associated First Person interview with the first author of the paper.

Keywords: Antimicrobial peptide; Bromodomain protein; Drosophila melanogaster; Insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / metabolism*
  • Enzyme Activation
  • Fat Body / metabolism
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation
  • Hypoglycemia / pathology
  • Insulin / metabolism
  • Longevity
  • Phenotype
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Survival Analysis
  • Transcription Factors / metabolism*
  • Triglycerides / metabolism


  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • Triglycerides
  • fs(1)h protein, Drosophila
  • Akt1 protein, Drosophila
  • Proto-Oncogene Proteins c-akt