Figure 1

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[88], Anthony et al.[89], Drummond et al.[61], Um et al.[98] 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.[70], Bodine et al.[99], Anthony et al.[89] and Blagosklonny et al.[62]. 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.