title: Dietary L-Lysine Suppresses Autophagic Proteolysis and Stimulates Akt/mTOR Signaling in the Skeletal Muscle of Rats Fed a Low-Protein Diet.
abstract: Amino acids, especially L-leucine, regulate protein turnover in skeletal muscle and have attracted attention as a means of increasing muscle mass in people suffering from malnutrition, aging (sarcopenia), or a bedridden state. We previously showed that oral administration of L-lysine (Lys) by gavage suppressed proteolysis in skeletal muscles of fasted rats. However, the intake of Lys in the absence of other dietary components is unlikely in a non-experimental setting, and other dietary components may interfere with the suppressive effect of Lys on proteolysis. We supplemented Lys to a 10% casein diet and investigated the effect of Lys on proteolysis and autophagy, a major proteolytic system, in the skeletal muscle of rats. The rate of proteolysis was evaluated from 3-methylhisitidine (MeHis) released from isolated muscles, in plasma, and excreted in urine. Supplementing lysine with the 10% casein diet decreased the rate of proteolysis induced by intake of a low-protein diet. The upregulated autophagy activity [light chain 3 (LC3)-II/total LC3] caused by a low-protein diet was reduced, and the Akt/mTOR signaling pathway was activated by Lys. Importantly, continuous feeding of a Lys-rich 10% casein diet for 15 days increased the masses of the soleus and gastrocnemius muscles. Taken together, supplementation of Lys to a low-protein diet suppresses autophagic proteolysis through the Akt/mTOR signaling pathway, and continuous feeding of a Lys-rich diet may increase skeletal muscle mass.
authors.affiliation: Department of Bioresources Science, The United Graduate School of Agricultural Sciences, and ‡Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University , Morioka, Iwate 020-8550, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Bioresources Science, The United Graduate School of Agricultural Sciences, and ‡Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University , Morioka, Iwate 020-8550, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Bioresources Science, The United Graduate School of Agricultural Sciences, and ‡Department of Biological Chemistry and Food Science, Graduate School of Agriculture, Iwate University , Morioka, Iwate 020-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002364:Caseins / Q000008:administration & dosage; D004032:Diet; D018753:Diet, Protein-Restricted; D008239:Lysine / Q000008:administration & dosage*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055948:Sarcopenia / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002364:Caseins; D009124:Muscle Proteins; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D008239:Lysine
keywords: Akt; autophagy; l-lysine; low-protein diet; mTOR; sarcopenia