title: Activating transcription factor 3 regulates immune and metabolic homeostasis.
abstract: Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.
authors.affiliation: Institute for Genetics and Cologne Excellence Cluster in Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rynes
authors.forename: Colin D
authors.initials: CD
authors.lastname: Donohoe
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.forename: Susanne
authors.initials: S
authors.lastname: Brodesser
authors.forename: Marek
authors.initials: M
authors.lastname: Jindra
authors.forename: Mirka
authors.initials: M
authors.lastname: Uhlirova
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D004063:Digestion; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development / Q000382:microbiology / Q000502:physiology*; D005223:Fats / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007109:Immunity; D050356:Lipid Metabolism; D009154:Mutation; D009765:Obesity / Q000235:genetics; D013217:Starvation / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; D029721:Drosophila Proteins; D005223:Fats