Dietary effects of early nutrition on muscle mass and accretion in mammals

Skeletal muscle serves as the primary protein reservoir in neonates and is a major determinant of early postnatal growth. This period features exceptionally high muscle protein synthesis, driven by increased sensitivity to feeding-induced insulin and amino acid signals that converge on the mechanistic target of rapamycin complex 1 (mTORC1). These signals regulate postnatal metabolic activation and anabolic responsiveness, rather than driving developmental transitions. This review summarizes the endocrine, nutrient-sensing, and energy-sensing pathways that regulate early-life skeletal muscle accretion, highlighting translational efficiency, ribosomal capacity, and myonuclear accretion as key determinants of growth. Evidence from translational neonatal models, particularly the pig, demonstrates coordinated control of muscle anabolism by insulin/IGF signaling, amino acid sensing, and cellular energy status, and shows how prematurity and intrauterine growth restriction disrupt these processes, resulting in anabolic resistance. Colostrum and milk support muscle growth primarily by enhancing intestinal maturation, nutrient delivery, and postprandial endocrine responses, whereas direct programming via milk-derived extracellular vesicles remains uncertain.