Abstract
Dietary supplementation with methionine and threonine spares body protein in rats fed a low protein diet, but the effect is not observed for other essential amino acids. Although the requirement for sulfur amino acids is relatively high in rodents, the precise mechanisms underlying protein retention are not fully understood. The aim of this study was to explore whether the activation of mammalian target of rapamycin complex 1 (mTORC1) downstream factors in skeletal muscle by supplementation with threonine and/or methionine contributes to protein retention under sufficient cystine requirement. Male Sprague–Dawley rats were freely fed a 0% protein diet for 2 weeks. These experimental rats were then fed a restricted diet (14.5 g/day) containing 12% soy protein supplemented with both cystine and, methionine and threonine (MT), methionine (M), threonine (T), or neither (NA) (n = 8) for an additional 12 days. Two additional groups were freely fed a diet containing 0% protein or 20% casein 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 was higher, and eukaryotic translation initiation factor 4E-binding protein 1 abundance and mRNA levels were lower, in the skeletal muscles of the M and MT groups. These results suggest that methionine regulates mTORC1 downstream factors in skeletal muscle, leading to spare body protein in rats fed a low protein diet meeting cystine requirements.
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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are grateful to Dr. K. Yagasaki and Dr. H. Oda (Nagoya University) for helpful insights and suggestions, and A. Nagahama and K. Suzuki for performing the LC/MS analysis. We thank all members of the Medical Foods Research Institute.
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All authors conceived the idea of the study. FY and IY developed the outline for the statistical analysis and conducted the statistical analyses. All authors contributed to the acquisition and analysis of the data and the interpretation of the results. FY drafted the original manuscript. IY reviewed the manuscript draft and revised it critically for intellectual content. All authors approved the final version of the manuscript to be published.
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All animals were treated in accordance with the guidelines established by the Animal Care and Use Committee of Otsuka Pharmaceutical Factory, Inc. (Tokushima, Japan). The experimental protocol was approved by the Animal Experimentation Committee of Otsuka Pharmaceutical Factory, Inc.
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Yamada, F., Mori, E. & Yamaoka, I. Methionine supplementation spares body protein by regulating the expression of mTORC1 downstream factors in rats fed a soy protein diet with sufficient sulfur amino acids: a pilot study. Amino Acids 55, 1039–1048 (2023). https://doi.org/10.1007/s00726-023-03291-4
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DOI: https://doi.org/10.1007/s00726-023-03291-4