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bioRxiv · 10.64898/2026.04.17.719133

The tongue-brain axis mediates a hidden amino acid appetite

Wu, S.·Gan, Y.·Tang, M.·Chen, S.·Luo, P.·Tong, K.·Liu, K.·Jiang, H.·Jiang, X.·Xiao, F.·Lv, W.·Yuan, F.·Guo, F.
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Abstract

Selecting a diet containing all essential amino acids (EAAs) is critical for health. Following EAA deprivation, animals can select a nutritiously complete food source; however, the underlying mechanisms in vertebrates remain unclear. In mice, we show that leucine deficiency activates hypothalamic agouti-related protein (AgRP) neurons, which project to the paraventricular thalamus (PVT) via {gamma}-aminobutyric acid and are required for EAA deficiency-induced leucine appetite in mice. Furthermore, the peripheral tongue amino acid sensor general control nonderepressive-2 (GCN2) mediates acute EAA appetite via AgRP neurons. Together, these findings identify a tongue-AgRP-PVT circuit underlying EAA appetite, which is important for the rapid and accurate selection of essential nutrients.

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Wu, S., Gan, Y., Tang, M., Chen, S., Luo, P., Tong, K., Liu, K., Jiang, H., Jiang, X., Xiao, F., Lv, W., Yuan, F., Guo, F.. 2026-04-21. The tongue-brain axis mediates a hidden amino acid appetite. https://doi.org/10.64898/2026.04.17.719133

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