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Uncovering how environmental cues regulate metabolism via the anti-growth hormone Adenosine

Objective

Animal growth is modulated by environmental cues such as nutrient availability or temperature. Animals integrate these cues through hormonal signals that coordinate growth and metabolism across tissues. One such system is the anabolic IGF/PI3K/mTORC1 pathway, which promotes growth. We discovered in Drosophila that the circulating metabolite adenosine is a potent anti-growth hormone which counter-balances the activity of IGF. Levels of circulating adenosine increase when dietary amino acids are low, leading to systemic inhibition of growth via activation of AMPK and consequently inhibition of mTORC1.

These initial findings raise several fundamental questions which need to be addressed to understand how adenosine mediates the effect of environmental cues on organismal growth and metabolism:

(1) What biochemical pathways and what tissues generate adenosine under physiological conditions?
(2) Which environmental and pathophysiological cues beyond amino acid scarcity regulate adenosine levels?
(3) How does adenosine-AMPK signaling reshape metabolism, given AMPK’s influence on fatty acid oxidation, autophagy, protein synthesis, and more?

This work will reveal how adenosine functions as a counterbalancing hormonal brake to the IGF/mTORC1- anabolic program, providing a new framework for understanding how animals achieve a homeostatic balance between pro-growth and anti-growth signals in response to environmental cues. These mechanisms will likely be conserved across insects, which represent 80% of animal species on earth. Furthermore, they will lay the groundwork for exploring in the future whether adenosine regulates mammalian physiology via AMPK in addition to its known receptor-mediated effects.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-ADG

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Host institution

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 499 587,00
Address
IM NEUENHEIMER FELD 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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