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Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033
4To whom correspondence should be addressed.
We investigated the protein synthetic response of skeletal muscle to an
orally administered dose of leucine given alone or in combination with
carbohydrate. Male rats were freely fed (F) or food deprived for
18 h; food-deprived rats were then administered saline (S),
carbohydrate (CHO), leucine (L) or a combination of carbohydrate plus
leucine (CL). CHO and CL meals were isocaloric and provided 15% of
daily energy requirements. L and CL meals each delivered 270 mg
leucine. Muscle protein synthesis in S was 65% of F (P
< 0.01) 1 h after meal administration. Concomitant with
lower rates of protein synthesis, phosphorylation of the translational
repressor, eukaryotic initiation factor (eIF)4E-binding protein 1
(4E-BP1), was less in S, leading to greater association of
4E-BP1·eIF4E, and reduced formation of the active eIF4G·eIF4E
complex compared with F (P < 0.01). Oral
administration of leucine (L or CL), but not CHO, restored protein
synthesis equal to that in F and resulted in 4E-BP1 phosphorylation
that was threefold greater than that of S (P < 0.01). Consequently, formation of 4E-BP1·eIF4E was inhibited and
eIF4G·eIF4E was not different from F. The amount of eIF4E in the
phosphorylated form was greater in S and CHO (P < 0.01) than in all other groups. In contrast, no differences in the
phosphorylation state of eIF2
or the activity of eIF2B were noted
among treatment groups. Serum insulin was elevated 2.6- and 3.7-fold in
CHO and CL, respectively, but was not different in L, compared with S
(P < 0.05). These results suggest that leucine
stimulates protein synthesis in skeletal muscle by enhancing eIF4F
formation independently of increases in serum insulin.
KEY WORDS: • leucine • protein synthesis • translation initiation • skeletal muscle • rats
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