PMID- 10720160 OWN - NLM STAT- MEDLINE DCOM- 20000330 LR - 20220227 IS - 0022-3166 (Print) IS - 0022-3166 (Linking) VI - 130 IP - 2 DP - 2000 Feb TI - Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. PG - 139-45 AB - 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 eIF2alpha 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. FAU - Anthony, J C AU - Anthony JC AD - Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey 17033, USA. FAU - Anthony, T G AU - Anthony TG FAU - Kimball, S R AU - Kimball SR FAU - Vary, T C AU - Vary TC FAU - Jefferson, L S AU - Jefferson LS LA - eng GR - DK-15658/DK/NIDDK NIH HHS/United States GR - GM-08619/GM/NIGMS NIH HHS/United States GR - GM-39277/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Dietary Carbohydrates) RN - 0 (Eukaryotic Initiation Factor-4F) RN - 0 (Muscle Proteins) RN - 0 (Peptide Initiation Factors) RN - GMW67QNF9C (Leucine) SB - IM MH - Administration, Oral MH - Animals MH - Dietary Carbohydrates/administration & dosage/*pharmacology MH - Eukaryotic Initiation Factor-4F MH - Food Deprivation MH - Leucine/administration & dosage/blood/*pharmacology MH - Male MH - Muscle Proteins/*biosynthesis MH - Muscle, Skeletal/*drug effects/*metabolism MH - Peptide Initiation Factors/*biosynthesis/drug effects/metabolism MH - Phosphorylation/drug effects MH - Rats MH - Rats, Sprague-Dawley EDAT- 2000/03/17 09:00 MHDA- 2000/04/01 09:00 CRDT- 2000/03/17 09:00 PHST- 2000/03/17 09:00 [pubmed] PHST- 2000/04/01 09:00 [medline] PHST- 2000/03/17 09:00 [entrez] AID - 10.1093/jn/130.2.139 [doi] PST - ppublish SO - J Nutr. 2000 Feb;130(2):139-45. doi: 10.1093/jn/130.2.139.