PMID- 12217901
OWN - NLM
STAT- MEDLINE
DCOM- 20021010
LR  - 20211203
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 283
IP  - 4
DP  - 2002 Oct
TI  - Tissue-specific effects of chronic dietary leucine and norleucine supplementation 
      on protein synthesis in rats.
PG  - E824-35
AB  - Acute administration of leucine and norleucine activates the mammalian target of 
      rapamycin (mTOR) cell-signaling pathway and increases rates of protein synthesis 
      in a number of tissues in fasted rats. Although persistent stimulation of mTOR 
      signaling is thought to increase protein synthetic capacity, little information 
      is available concerning the effects of chronic administration of these agonists 
      on protein synthesis, mTOR signal transduction, or leucine metabolism. Hence, we 
      developed a model of chronic leucine/norleucine supplementation via drinking 
      water and examined the effects of chronic (12 days) supplementation on protein 
      synthesis in adipose tissue, kidney, heart, liver, and skeletal muscle from ad 
      libitum-fed rats. The relative concentration of proteins involved in mTOR 
      signaling and the two initial steps in leucine oxidation were also examined. 
      Leucine or norleucine supplementation was accompanied by increased rates of 
      protein synthesis in adipose tissue, liver, and skeletal muscle, but not in heart 
      or kidney. Supplementation was not associated with increases in the anabolic 
      hormones insulin or insulin-like growth factor I. Chronic supplementation did not 
      cause apparent adaptation in either components of the mTOR cell-signaling pathway 
      that respond to leucine (mTOR, ribosomal protein S6 kinase, and eukaryotic 
      initiation factor 4E-binding protein-1) or the first two steps in leucine 
      metabolism (the mitochondrial isoform of branched-chain amino acid transaminase, 
      branched-chain keto acid dehydrogenase, and branched-chain keto acid 
      dehydrogenase kinase), which may be involved in terminating the signal from 
      leucine. These results suggest that provision of leucine or norleucine 
      supplementation via the drinking water results in stimulation of postprandial 
      protein synthesis in adipose tissue, skeletal muscle, and liver without notable 
      adaptive changes in signaling proteins or metabolic enzymes.
FAU - Lynch, Christopher J
AU  - Lynch CJ
AD  - Department of Cellular and Molecular Physiology, Pennsylvania State University 
      College of Medicine, Hershey, Pennsylvania 17033, USA. clynch@psu.edu
FAU - Hutson, Susan M
AU  - Hutson SM
FAU - Patson, Brian J
AU  - Patson BJ
FAU - Vaval, Alain
AU  - Vaval A
FAU - Vary, Thomas C
AU  - Vary TC
LA  - eng
GR  - AA-12814/AA/NIAAA NIH HHS/United States
GR  - DK-34738/DK/NIDDK NIH HHS/United States
GR  - DK-53843/DK/NIDDK 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, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Amino Acids)
RN  - 0 (Leptin)
RN  - 0 (Multienzyme Complexes)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 832C8OV84S (Norleucine)
RN  - EC 1.2.- (Ketone Oxidoreductases)
RN  - EC 1.2.4.4 (3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide))
RN  - EC 2.6.1.- (Transaminases)
RN  - EC 2.6.1.42 (branched-chain-amino-acid transaminase)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Ptk2b protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
MH  - Adipose Tissue/metabolism
MH  - Amino Acid Sequence
MH  - Amino Acids/blood
MH  - Animals
MH  - Body Weight/drug effects
MH  - Drinking/drug effects
MH  - Eating/drug effects
MH  - Focal Adhesion Kinase 2
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Ketone Oxidoreductases/metabolism
MH  - Leptin/blood
MH  - Leucine/*pharmacology
MH  - Liver/metabolism
MH  - Male
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/metabolism
MH  - Muscle, Skeletal/metabolism
MH  - Norleucine/*pharmacology
MH  - *Protein Biosynthesis
MH  - Protein Kinases/metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Tissue Distribution
MH  - Transaminases/metabolism
EDAT- 2002/09/10 10:00
MHDA- 2002/10/11 04:00
CRDT- 2002/09/10 10:00
PHST- 2002/09/10 10:00 [pubmed]
PHST- 2002/10/11 04:00 [medline]
PHST- 2002/09/10 10:00 [entrez]
AID - 10.1152/ajpendo.00085.2002 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E824-35. doi: 
      10.1152/ajpendo.00085.2002.