title: The Drosophila TNF Eiger Is an Adipokine that Acts on Insulin-Producing Cells to Mediate Nutrient Response.
abstract: Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation.
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Neha
authors.initials: N
authors.lastname: Agrawal
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Renald
authors.initials: R
authors.lastname: Delanoue
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mauri
authors.affiliation: Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Basco
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Pasco
authors.affiliation: Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.affiliation: Université Nice Sophia Antipolis, CNRS, Inserm, iBV, 06100 Nice, France. Electronic address: leopold@unice.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Léopold
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D049628:Body Size; D002460:Cell Line; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005508:Food Deprivation; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D054392:Adipokines; D029721:Drosophila Proteins; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha