Dietary protein, muscle and the fat-free mass within the Protein-Stat control framework: Blaxter Award Lecture 2025.

My research on dietary protein and the regulation of proteostasis in muscle and the whole body during growth and adult maintenance is reviewed. Growth control involves both permissive and regulatory roles of protein acting with genetic determinants and functional demand, to mediate substrate flow into metabolic consumption, energy storage and growth. In 1995 a Protein-Stat hierarchical model for control of the fat-free mass was proposed and is updated here with special emphasis on the skeletal muscle mass. Control is exerted in large part through a central aminostatic appetite mechanism sensing changes in free amino-acid patterns in response to the balance between their supply in relation to their demand. This acts primarily to maintain skeletal muscle mass at a level set by the linear dimensions of the organism, which in turn is controlled by genetic programming and mediated by the developmental hormones acting together with an appropriate anabolic drive deriving from dietary protein. This, together with other important nutrients like zinc, calcium and vitamin D, provides the regulatory stimulus for growth and protein deposition in all tissues. The applicability of this model to childhood growth and development will be described as well as the maintenance of the adult phenotypic muscle mass within populations with protein intakes varying over a wide range, work which resulted in an adaptive metabolic demand model for protein and amino acid requirements and values for apparent adult protein and lysine requirements. Finally current understanding of aminostatic mechanisms of amino-acid sensing in the brain will be reviewed.