Regulation of muscle growth in neonates

Abstract

Purpose of review: This review reports recent findings on the multiple factors that regulate skeletal muscle growth in neonates.

Recent findings: Skeletal muscle is the fastest growing protein mass in neonates. The high rate of neonatal muscle growth is due to accelerated rates of protein synthesis accompanied by the rapid accumulation of muscle nuclei. Feeding profoundly stimulates muscle protein synthesis in neonates and the response decreases with age. The feeding-induced stimulation of muscle protein synthesis is modulated by enhanced sensitivity to the postprandial rise in insulin and amino acids. Insulin and amino acid signaling components have been identified that are involved in the feeding-induced stimulation of protein synthesis in neonatal muscle. The enhanced activation of these signaling components in skeletal muscle of the neonate contributes to the high rate of muscle protein synthesis and rapid gain in muscle protein mass in neonates.

Summary: Recent findings suggest that the immature muscle has a heightened capacity to activate signaling cascades that promote translation initiation in response to the postprandial rise in insulin and amino acids thereby enabling their efficient utilization for muscle growth. This capacity is further supported by enhanced satellite cell proliferation, but how these two processes are linked remains to be established.

Figure 1. Muscle protein accretion in early postnatal life

(a) Relative changes in the proportion of whole-body protein mass attributable to skeletal muscle protein in the rat between birth and weaning (Fiorotto et al., unpublished observations). (b) Relationship between the postnatal change in the rate of muscle protein accretion and the fractional rates of protein synthesis and degradation in skeletal muscle proteins during the suckling period in the hind limb muscles of rats [2,3]. , Fractional synthesis rate; , fractional accretion rate; , fractional degradation rate.

Figure 2. Insulin and amino acid signaling pathways that lead to translation initiation

4EBP1, 4E-binding protein 1; AMPK, AMP-activated protein kinase; mTOR, mammalian target of rapamycin; PDK1, phosphoinositide-dependent kinase 1; PI3-K, phosphatidylinositol 3-kinase; PKB, protein kinase B; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homologue deleted on chromosome 10; PTP1B, protein tyrosine phosphatase 1B; TSC, tuberous sclerosis complex.

Figure 3. Regulation of translation initiation

4EBP1, 4E-binding protein 1; GDP, guanosine diphosphate; GTP, guanosine triphosphate.

Figure 4. The relative consequence of suboptimal nutrition during the suckling period on total protein content and the ratio of protein to DNA in various hind limb muscles of weanling rats

Data were compiled from three studies: (a) [81], (b) [82], (c) [3]. EDL, extensor digitorum longus; Gastroc, gastrocnemius muscle; SOL, soleus. ■, Total protein; ▨, protein : DNA.