Journal
CELL METABOLISM
Volume 23, Issue 4, Pages 675-684Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2016.03.003
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Funding
- CNRS
- INSERM
- European Research Council [268813]
- Labex Signalife program [ANR-11-LABX-0028-01]
- European Research Council (ERC) [268813] Funding Source: European Research Council (ERC)
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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-alpha, 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-alpha 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-alpha that mediates adaptive response to nutrient deprivation.
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