Yoshinari Yuto, Nishimura Takashi, Yoshii Taishi, Kondo Shu, Tanimoto Hiromu, Kobayashi Tomoe, Matsuyama Makoto, Niwa Ryusuke
Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8577, Japan.
Nat Commun. 2024 Dec 30;15(1):10819. doi: 10.1038/s41467-024-55050-y.
Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload.
蛋白质对所有生物都至关重要；然而，蛋白质摄入过多会产生不良影响，如高氨血症。尽管对蛋白质缺乏的反应机制已有充分研究，但我们对生物体如何适应性抑制过量蛋白质摄入的理解仍存在重大差距。在本研究中，我们利用果蝇（黑腹果蝇）发现，肠道内分泌细胞在高蛋白饮食（HPD）刺激下分泌的肽激素CCHamide1（CCHa1），对抑制蛋白质过度摄入至关重要。肠道来源的CCHa1被一小部分产生短神经肽F的肠神经元接收，从而调节蛋白质特异性饱腹感。重要的是，在HPD条件下，CCHa1介导的肠道 - 肠神经元轴受损会导致氨积累和寿命缩短。总之，我们的研究结果揭示了肠道激素和神经元通路之间的相互作用，这些相互作用协调生理反应以预防和适应饮食蛋白质过载。
