4.6 Review

Amino Acid Sensing in Metabolic Homeostasis and Health

Journal

ENDOCRINE REVIEWS
Volume 42, Issue 1, Pages 56-76

Publisher

ENDOCRINE SOC
DOI: 10.1210/endrev/bnaa026

Keywords

amino acids; sensing signals; metabolic homeostasis; mTORC1; GCN2

Funding

  1. National Key R&D Program of China [2018YFA0800600]
  2. National Natural Science Foundation [91957207, 31830044, 81870592, 81970731, 81970742, 81770852, 81700761, 81700750]
  3. CAS Interdisciplinary Innovation Team
  4. Novo Nordisk-Chinese Academy of Sciences Research Fund [NNCAS-2008-10]
  5. Youth Innovation Promotion Association CAS

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The body's ability to sense and respond to changes in nutrient levels, particularly amino acids, is crucial for survival. Amino acids play dual roles as building blocks for proteins and peptides, as well as important bioactive molecules involved in signaling pathways and metabolic regulation. Imbalance in amino acid sensing signals may be linked to metabolic disorders, highlighting their potential as therapeutic targets.
Sensing and responding to changes in nutrient levels, including those of glucose, lipids, and amino acids, by the body is necessary for survival. Accordingly, perturbations in nutrient sensing are tightly linked with human pathologies, particularly metabolic diseases such as obesity, type 2 diabetes mellitus, and other complications of metabolic syndromes. The conventional view is that amino acids are fundamental elements for protein and peptide synthesis, while recent studies have revealed that amino acids are also important bioactive molecules that play key roles in signaling pathways and metabolic regulation. Different pathways that sense intracellular and extracellular levels of amino acids are integrated and coordinated at the organismal level, and, together, these pathways maintain whole metabolic homeostasis. In this review, we discuss the studies describing how important sensing signals respond to amino acid availability and how these sensing mechanisms modulate metabolic processes, including energy, glucose, and lipid metabolism. We further discuss whether dysregulation of amino acid sensing signals can be targeted to promote metabolic disorders, and discuss how to translate these mechanisms to treat human diseases. This review will help to enhance our overall understanding of the correlation between amino acid sensing and metabolic homeostasis, which have important implications for human health.

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