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Biochemical and Molecular Actions of Nutrients

Oral Leucine Administration Stimulates Protein Synthesis in Rat Skeletal Muscle¹

Stephen J. Crozier^*, Scot R. Kimball^*, Sans W. Emmert^*, Joshua C. Anthony and Leonard S. Jefferson^*,2

^* Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033 and Mead Johnson Nutritionals, Evansville, IN 47721

²To whom correspondence should be addressed. E-mail: jjefferson{at}psu.edu.

Oral administration of a single bolus of leucine in an amount equivalent to the daily intake (1.35 g/kg body wt) enhances skeletal muscle protein synthesis in food-deprived rats. To elucidate whether smaller amounts of leucine can also stimulate protein synthesis, rats were administered the amino acid at concentrations ranging from 0.068 to 1.35 g/kg body wt by oral gavage. Thirty minutes following the administration of doses of leucine as low as 0.135 g/kg body wt, skeletal muscle protein synthesis was significantly greater than control values. The increase in protein synthesis was associated with changes in the regulation of biomarkers of mRNA translation initiation as evidenced by upregulated phosphorylation of the translational repressor, eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), the association of eIF4G with the mRNA cap binding protein eIF4E, and the phosphorylation of the 70-kDa ribosomal protein S6 kinase. Alterations in the phosphorylation of eIF4G, as well as the association of 4E-BP1 with eIF4E, were observed following leucine administration; however, these changes appeared to be biphasic with maximal changes occurring when circulating insulin concentrations were elevated. Thus it appears that leucine administration affects mRNA translation and skeletal muscle protein synthesis through modulation of multiple biomarkers of mRNA translation. The ability of small doses of leucine to stimulate skeletal muscle protein synthesis suggests that future research on the regulation of skeletal muscle protein synthesis by orally administered leucine will be feasible in humans.

KEY WORDS: • translation initiation • gastrocnemius muscle • mTOR

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