title: Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. clynch@psu.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lynch
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hutson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Patson
authors.forename: Alain
authors.initials: A
authors.lastname: Vaval
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Vary
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000273:Adipose Tissue / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D051418:Focal Adhesion Kinase 2; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism; D020738:Leptin / Q000097:blood; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009646:Norleucine / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014018:Tissue Distribution; D000637:Transaminases / Q000378:metabolism
chemical_list: D000596:Amino Acids; D020738:Leptin; D009097:Multienzyme Complexes; D007334:Insulin-Like Growth Factor I; D009646:Norleucine; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D011494:Protein Kinases; C546845:mTOR protein, rat; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine