A schematic representation depicting A; the protein synthesis pathway in skeletal muscle involving the mammalian target of rapamycin complex 1 (mTORC1). Insulin, and amino acids (including leucine) initiate activation of a cascade of protein and lipid kinases ultimately resulting in enhanced mTOR activity, facilitating the phosphorylation of S6K1 and hyper-phosphorylation of 4E-BP, resulting in enhanced availability of eIF4E for binding eIF4G and forming an active eIF4F complex resulting in increased protein synthesis [adapted from Layman, Anthony et al., Drummond et al., Um et al. and Kimball[90, 93] and B; our proposed mechanism whereby high protein calorie restricted weight loss increases IGF-1 activating the PI3K/Akt pathway, thereby phosphorylating (P) FoxO transcription factors and down-regulating the expression of E3 enzymes atrogin-1 and MuRF-1, leading to a reduction in protein degradation in skeletal muscle cells. PGC-1α, SIRT1 and AMPK are also proposed to inhibit the expression of FoxO transcription factors and therefore suppress protein breakdown [adapted from Lecker et al., Bodine et al., Anthony et al. and Blagosklonny et al.. Dashed lines indicate an interaction with an unknown mechanism. Red lines indicate an inhibitory signal to the pathway, and C; Summarisation of protein biosynthetic and degradation events following standard protein, high carbohydrate compared to high protein, calorie restricted weight loss.