Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
RIKEN Center for Biosystems and Dynamics Research, Kobe, Japan.
Nat Metab. 2022 Jul;4(7):944-959. doi: 10.1038/s42255-022-00608-7. Epub 2022 Jul 25.
The intake of dietary protein regulates growth, metabolism, fecundity and lifespan across various species, which makes amino acid (AA)-sensing vital for adaptation to the nutritional environment. The general control nonderepressible 2 (GCN2)-activating transcription factor 4 (ATF4) pathway and the mechanistic target of rapamycin complex 1 (mTORC1) pathway are involved in AA-sensing. However, it is not fully understood which AAs regulate these two pathways in living animals and how they coordinate responses to protein restriction. Here we show in Drosophila that the non-essential AA tyrosine (Tyr) is a nutritional cue in the fat body necessary and sufficient for promoting adaptive responses to a low-protein diet, which entails reduction of protein synthesis and mTORC1 activity and increased food intake. This adaptation is regulated by dietary Tyr through GCN2-independent induction of ATF4 target genes in the fat body. This study identifies the Tyr-ATF4 axis as a regulator of the physiological response to a low-protein diet and sheds light on the essential function of a non-essential nutrient.
饮食蛋白质的摄入可调节多种物种的生长、代谢、繁殖力和寿命，这使得氨基酸（AA）感应对于适应营养环境至关重要。一般控制非阻遏 2（GCN2）激活转录因子 4（ATF4）途径和雷帕霉素复合物 1（mTORC1）途径参与 AA 感应。然而，尚不完全清楚哪些 AA 在活体动物中调节这两条途径，以及它们如何协调对蛋白质限制的反应。在这里，我们在果蝇中表明，非必需氨基酸酪氨酸（Tyr）是脂肪体中的一种营养信号，对于促进对低蛋白饮食的适应性反应是必要和充分的，这需要减少蛋白质合成和 mTORC1 活性，并增加食物摄入。这种适应受饮食 Tyr 通过 GCN2 独立诱导脂肪体中 ATF4 靶基因来调节。这项研究确定了 Tyr-ATF4 轴作为低蛋白饮食生理反应的调节剂，并揭示了非必需营养素的重要功能。
