Methionine mitigates protein deficiency by regulating the expression of translation initiation factors, even with sufficient sulfur, in rats fed a protein-deprived diet

Dietary supplementation with methionine and threonine mitigates protein deficiency in rats fed a protein-deprived diet, an effect that is not observed for other essential amino acids. However, the precise mechanisms are not fully understood. The aim of this study was to explore whether the activation of translation initiation factors in the mammalian target of rapamycin pathway in skeletal muscle contributes to protein retention by supplementation with methionine and/or threonine. Male Sprague-Dawley rats were freely fed 0% protein diets for 2 weeks, and furthermore fed for 12 days 14.5 g of a restricted diet containing 12% soy protein supplemented with methionine and threonine (MT), methionine (M), threonine (T), or neither (NA) (n = 8), while two additional groups were fed 0% protein or 20% casein protein diets as controls (n = 6). Body weight and gastrocnemius muscle weight were higher, and blood urea nitrogen and urinary nitrogen excretion were lower, in the M and MT groups than in the T and NA groups, respectively. p70 S6 kinase 1 abundance and protein expression levels were higher, and eukaryotic translation initiation factor 4E-binding protein 1 abundance and mRNA levels were lower, in the skeletal muscles of rats fed with methionine (M and MT groups). These results suggest that methionine regulates the mass of protein via translation initiation machinery in the skeletal muscle, retaining whole-body protein in protein-deprived rats.