Perspective: The Potential Role of Essential Amino Acids and the Mechanistic Target of Rapamycin Complex 1 (mTORC1) Pathway in the Pathogenesis of Child Stunting

Abstract

Stunting is the best summary measure of chronic malnutrition in children. Approximately one-quarter of children under age 5 worldwide are stunted. Lipid-based or micronutrient supplementation has little to no impact in reducing stunting, which suggests that other critical dietary nutrients are missing. A dietary pattern of poor-quality protein is associated with stunting. Stunted children have significantly lower circulating essential amino acids than do nonstunted children. Inadequate dietary intakes of essential amino acids could adversely affect growth, because amino acids are required for synthesis of proteins. The master growth regulation pathway, the mechanistic target of rapamycin complex 1 (mTORC1) pathway, is exquisitely sensitive to amino acid availability. mTORC1 integrates cues such as nutrients, growth factors, oxygen, and energy to regulate growth of bone, skeletal muscle, nervous system, gastrointestinal tract, hematopoietic cells, immune effector cells, organ size, and whole-body energy balance. mTORC1 represses protein and lipid synthesis and cell and organismal growth when amino acids are deficient. Over the past 4 decades, the main paradigm for child nutrition in developing countries has been micronutrient malnutrition, with relatively less attention paid to protein. In this Perspective, we present the view that essential amino acids and the mTORC1 pathway play a key role in child growth. The current assumption that total dietary protein intake is adequate for growth among most children in developing countries needs reevaluation. Adv Nutr 2016;7:853-65.

Associations among High-Quality Protein and Energy Intake, Serum Transthyretin, Serum Amino Acids and Linear Growth of Children in Ethiopia

“…There are several possible explanations for these positive associations. First, protein and amino acids have biological roles in protein and lipid synthesis, bone elongation, and the regulation of these and other processes necessary for linear growth [ 9 , 11 , 58 ]. Secondly, sufficient availability of amino acids potentially regulates cell and organismal growth [ 11 ].…”

“…Protein and essential amino acids are required for the growth of children [ 9 , 10 , 11 ]. The association between children’s growth and high-quality protein intake (particularly intake of limiting essential amino acids lysine and tryptophan) is complex and influenced by several factors (see Figure 1 ).…”

The Rise and Fall of Protein Malnutrition in Global Health

“…The availability of amino acids is sensed via the master growth regulatory pathway of the cell, the mechanistic target of rapamycin complex 1 (mTORC1) [51, 52] and by a related amino acid sensing pathway, the general control nonderepressible 2 (GCN2) pathway [53]. mTORC1 integrates environmental cues such as nutrients, growth factors, oxygen, and energy to regulate growth and homeostasis.…”

“…mTORC1 integrates environmental cues such as nutrients, growth factors, oxygen, and energy to regulate growth and homeostasis. mTORC1 will repress protein and lipid synthesis and cell and organismal growth when amino acids are deficient [52]. …”

Comparison of Cognitive and Other Developmental Functions in Children With Stunting and Malnutrition

“…mTORC1 is very sensitive to the availability of essential amino acids for its activation, because growth factors and energy cannot overcome the lack of essential amino acids to activate mTORC1. 19…”