Tsang Anthony H, Samson Liubou, Blouet Clemence
Institute of Metabolic Science-Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit at the University of Cambridge, Cambridge, UK.
Open Biol. 2025 Aug;15(8):250092. doi: 10.1098/rsob.250092. Epub 2025 Aug 6.
Amino acids are essential for normal physiological functions, and disruptions in their circulating concentrations are implicated in the pathophysiology of various diseases. Therefore, understanding the mechanisms that regulate circulating amino acid levels in normal physiology is of critical importance. Evidence indicates that in healthy mammals, post-absorptive circulating levels of essential amino acids are maintained within a range that varies little from day to day or following bidirectional changes in dietary protein intake. This suggests the presence of homeostatic control mechanisms. Here, we propose a conceptual framework for the homeostatic regulation of essential amino acid availability, emphasizing the role of the brain in generating feedback controls to restore baseline levels acutely after a meal and during chronic changes in dietary protein intake. We review current evidence supporting brain amino acid sensing as a component of this regulatory system, integrating peripheral and central signals to modulate dietary protein intake and peripheral amino acid metabolism. We highlight major knowledge gaps regarding the specific neural circuits, molecular mechanisms and physiological outcomes of brain amino acid sensing. Future inquiry using the proposed framework and addressing these gaps will significantly enhance our understanding of the pathways involved in the maintenance of circulating amino acid availability and the regulation of lean mass in health, disease states or in response to therapeutic strategies for metabolic diseases.
氨基酸对于正常生理功能至关重要，其循环浓度的紊乱与多种疾病的病理生理学有关。因此，了解正常生理状态下调节循环氨基酸水平的机制至关重要。有证据表明，在健康哺乳动物中，吸收后必需氨基酸的循环水平维持在一个范围内，该范围在每日之间或饮食蛋白质摄入量双向变化后变化很小。这表明存在稳态控制机制。在此，我们提出一个必需氨基酸可利用性稳态调节的概念框架，强调大脑在进食后和饮食蛋白质摄入量长期变化期间产生反馈控制以急性恢复基线水平方面的作用。我们综述了支持大脑氨基酸感知作为该调节系统组成部分的现有证据，整合外周和中枢信号以调节饮食蛋白质摄入量和外周氨基酸代谢。我们强调了关于大脑氨基酸感知的特定神经回路、分子机制和生理结果的主要知识空白。未来使用所提出的框架并解决这些空白的研究将显著增强我们对维持循环氨基酸可利用性以及健康、疾病状态下或对代谢性疾病治疗策略反应中瘦体重调节所涉及途径的理解。
