Post-natal muscle growth and protein turnover: a narrative review of current understanding

Abstract

A model explaining the dietary-protein driven post-natal skeletal muscle growth and protein turnover in the rat is updated, and the mechanisms involved described in this narrative review. Dietary protein controls both length and muscle growth which are interrelated through mechanotransduction mechanisms with muscle growth induced by both stretching subsequent to bone length growth and from internal work against gravity. This induces satellite cell activation, myogenesis and remodeling of the extracellular matrix, establishing a growth capacity for myofibre length and cross-sectional area. Protein deposition within this capacity is enabled by adequate dietary protein and other key nutrients. After briefly reviewing the experimental animal origins of the growth model, key concepts and processes important for growth are reviewed. These include the growth in number and size of the myonuclear domain, satellite cell activity during post-natal development and the autocrine/paracrine action of IGF-1. Regulatory and signalling pathways reviewed include developmental mechanotransduction; signalling through the insulin/IGF-1-PI3K-Akt and the Ras-MAPK pathways in the myofibre and during mechanotransduction of satellite cells. Likely pathways activated by maximal-intensity muscle contractions are highlighted and the regulation of the capacity for protein synthesis in terms of ribosome assembly and the translational regulation of 5-TOPmRNA classes by mTORC1 and LARP1 are discussed. Evidence for and potential mechanisms by which volume limitation of muscle growth can occur which would limit protein deposition within the myofibre is reviewed. An understanding of how muscle growth is achieved allows better nutritional management of its growth in health and disease.

Post-prandial tracer studies of protein and amino acid utilisation: what can they tell us about human amino acid and protein requirements?

“…Thus, the existent of an upper limit to post-prandial protein deposition in both children and adults can be considered firmly established by the phenomenology of both childhood growth to adulthood and studies of healthy adult populations and their dietary protein intakes discussed above. Clearly although information is emerging on the mechanisms involved in such limitation of post-prandial protein deposition from both animal and human studies especially of MPS (42,44,120) , much remains to be revealed. The studies of leucine oxidation in response to feeding increasing protein intakes (105,106) suggest that utilisation was falling at the higher intakes fed in these subjects.…”

“…The key feature of the protein-stat concept is the interaction between bone length growth and appendicular muscle mass, whereby a phenotypical specific capacity for muscle growth is established through mechanotransduction mechanisms. Thus, the diurnal cycle of post-absorptive losses and post-prandial gains will occur to maintain muscle mass at the maximum, phenotypically controlled level, at which further protein deposition in muscle is limited by a 'bag full' signal (42)(43)(44) . Any additional protein intake above the habitual level can be deposited within the splanchnic tissues to a limited extent and will then be diverted to lipogenesis and adipose tissue expansion.…”

“…This showed that adaptation of amino acid oxidation to a change in protein intake was slow and incomplete over the short time period of our studies and involved some transient weight loss while the adaptation was occurring. These and other human studies, together with animal studies of the regulation of muscle growth (42) , resulted in the formulation of a 'protein-stat' mechanism for the regulation of growth and maintenance of the lean body mass explaining the interaction between dietary protein intake and whole body and muscle protein homoeostasis and growth (43) , which has recently been updated in the context of childhood growth and development (44) .…”

Effects of Amino Acid Supplementation to a Low-Protein Diet on the Growth Performance and Protein Metabolism-related Factors in Broiler Chicks

“…Skeletal muscle mass is regulated by the balance between protein synthesis and degradation[ 6 , 7 ], and is governed by anabolic hormones, such as insulin-like growth factor (IGF)-1, and catabolic hormones, such as glucocorticoids[ 8 , 9 , 10 ]. For example, IGF-1 treatment promotes hypertrophy of C2C12 myotubes[ 11 ] and proliferation of chick embryonic myoblasts[ 12 ].…”