Differential effects of long-term leucine infusion on tissue protein synthesis in neonatal pigs |
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Authors: | Fiona A Wilson Agus Suryawan Renán A Orellana María C Gazzaneo Hanh V Nguyen Teresa A Davis |
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Institution: | (1) Department of Pediatrics, Baylor College of Medicine, United States Department of Agriculture/Agriculture Research Service Children’s Nutrition Research Center, Houston, TX 77030, USA; |
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Abstract: | Leucine is unique among the amino acids in its ability to promote protein synthesis by activating translation initiation via
the mammalian target of rapamycin (mTOR) pathway. Previously, we showed that leucine infusion acutely stimulates protein synthesis
in fast-twitch glycolytic muscle of neonatal pigs but this response cannot be maintained unless the leucine-induced fall in
amino acids is prevented. To determine whether leucine can stimulate protein synthesis in muscles of different fiber types
and in visceral tissues of the neonate in the long-term if baseline amino acid concentrations are maintained, overnight fasted
neonatal pigs were infused for 24 h with saline, leucine (400 μmol kg−1 h−1), or leucine with replacement amino acids to prevent the leucine-induced hypoaminoacidemia. Changes in the fractional rate
of protein synthesis and activation of mTOR, as determined by eukaryotic initiation factor 4E binding protein (4E-BP1) and
S6 kinase 1 (S6K1) phosphorylation, in the gastrocnemius and masseter muscles, heart, liver, jejunum, kidney, and pancreas
were measured. Leucine increased mTOR activation in the gastrocnemius and masseter muscles, liver, and pancreas, in both the
absence and presence of amino acid replacement. However, protein synthesis in these tissues was increased only when amino
acids were infused to maintain baseline levels. There were no changes in mTOR signaling or protein synthesis in the other
tissues we examined. Thus, long-term infusion of leucine stimulates mTOR signaling in skeletal muscle and some visceral tissues
but the leucine-induced stimulation of protein synthesis in these tissues requires sustained amino acid availability. |
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