PMID- 20237068
OWN - NLM
STAT- MEDLINE
DCOM- 20100504
LR  - 20230216
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Print)
IS  - 0022-3166 (Linking)
VI  - 140
IP  - 5
DP  - 2010 May
TI  - Alcohol-induced IGF-I resistance is ameliorated in mice deficient for 
      mitochondrial branched-chain aminotransferase.
PG  - 932-8
LID - 10.3945/jn.109.120501 [doi]
AB  - Acute alcohol intoxication decreases skeletal muscle protein synthesis by 
      impairing mammalian target of rapamycin (mTOR). In 2 studies, we determined 
      whether inhibition of branched-chain amino acid (BCAA) catabolism ameliorates the 
      inhibitory effect of alcohol on muscle protein synthesis by raising the plasma 
      BCAA concentrations and/or by improving the anabolic response to insulin-like 
      growth factor (IGF)-I. In the first study, 4 groups of mice were used: wild-type 
      (WT) and mitochondrial branched-chain aminotransferase (BCATm) knockout (KO) mice 
      orally administered saline or alcohol (5 g/kg, 1 h). Protein synthesis was 
      greater in KO mice compared with WT controls and was associated with greater 
      phosphorylation of eukaryotic initiation factor (eIF)-4E binding protein-1 
      (4EBP1), eIF4E-eIF4G binding, and 4EBP1-regulatory associated protein of mTOR 
      (raptor) binding, but not mTOR-raptor binding. Alcohol decreased protein 
      synthesis in WT mice, a change associated with less 4EBP1 phosphorylation, 
      eIF4E-eIF4G binding, and raptor-4EBP1 binding, but greater mTOR-raptor complex 
      formation. Comparable alcohol effects on protein synthesis and signal 
      transduction were detected in BCATm KO mice. The second study used the same 4 
      groups, but all mice were injected with IGF-I (25 microg/mouse, 30 min). Alcohol 
      impaired the ability of IGF-I to increase muscle protein synthesis, 4EBP1 and 
      70-kilodalton ribosomal protein S6 kinase-1 phosphorylation, eIF4E-eIF4G binding, 
      and 4EBP1-raptor binding in WT mice. However, in alcohol-treated BCATm KO mice, 
      this IGF-I resistance was not manifested. These data suggest that whereas the 
      sustained elevation in plasma BCAA is not sufficient to ameliorate the catabolic 
      effect of acute alcohol intoxication on muscle protein synthesis, it does improve 
      the anabolic effect of IGF-I.
FAU - Lang, Charles H
AU  - Lang CH
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, PA 17033, USA. clang@psu.edu
FAU - Lynch, Christopher J
AU  - Lynch CJ
FAU - Vary, Thomas C
AU  - Vary TC
LA  - eng
GR  - GM38032/GM/NIGMS NIH HHS/United States
GR  - R01 AA011290/AA/NIAAA NIH HHS/United States
GR  - R01 DK062880/DK/NIDDK NIH HHS/United States
GR  - DK062880/DK/NIDDK NIH HHS/United States
GR  - GM39277/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100317
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (Eukaryotic Initiation Factor-4G)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Muscle Proteins)
RN  - 3K9958V90M (Ethanol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.6.1.- (Transaminases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Alcoholic Intoxication/genetics/*metabolism
MH  - Amino Acids, Branched-Chain/blood/*metabolism
MH  - Animals
MH  - Ethanol
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Eukaryotic Initiation Factor-4F/*metabolism
MH  - Eukaryotic Initiation Factor-4G/metabolism
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/enzymology
MH  - Muscle Proteins/*biosynthesis
MH  - Muscle, Skeletal/metabolism
MH  - Mutation
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Transaminases/*deficiency/genetics/metabolism
PMC - PMC2855262
EDAT- 2010/03/20 06:00
MHDA- 2010/05/05 06:00
PMCR- 2011/05/01
CRDT- 2010/03/19 06:00
PHST- 2010/03/19 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2010/05/05 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - S0022-3166(22)07052-3 [pii]
AID - 120501 [pii]
AID - 10.3945/jn.109.120501 [doi]
PST - ppublish
SO  - J Nutr. 2010 May;140(5):932-8. doi: 10.3945/jn.109.120501. Epub 2010 Mar 17.