title: Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach.
abstract: Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia. However, hyper-activation of mTOR/S6K1 has been suggested to inhibit the first steps of insulin signaling and finally promote insulin resistance. The impact of long-term dietary leucine supplementation on insulin signaling and sensitivity was investigated in old rats (18 months old) fed a 15% protein diet supplemented (LEU group) or not (C group) with 4.5% leucine for 6 months. The resulting effects on muscle and fat were examined. mTOR/S6K1 signaling pathway was not significantly altered in muscle from old rats subjected to long-term dietary leucine excess, whereas it was increased in adipose tissue. Overall glucose tolerance was not changed but insulin-stimulated glucose transport was improved in muscles from leucine-supplemented rats related to improvement in Akt expression and phosphorylation in response to food intake. No change in skeletal muscle mass was observed, whereas perirenal adipose tissue mass accumulated (+45%) in leucine-supplemented rats. A prolonged leucine supplementation in old rats differently modulates mTOR/S6K pathways in muscle and adipose tissue. It does not increase muscle mass but seems to promote hypertrophy and hyperplasia of adipose tissue that did not result in insulin resistance.
authors.affiliation: Centre Hospitalier Universitaire de Nice, Pôle Digestif, Nice, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Zeanandin
authors.forename: Michèle
authors.initials: M
authors.lastname: Balage
authors.forename: Stéphane M
authors.initials: SM
authors.lastname: Schneider
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mothe-Satney
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D015153:Blotting, Western; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D019893:Ribosomal Protein S6 Kinases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D055948:Sarcopenia / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D007328:Insulin; D012313:RNA; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D005947:Glucose