title: Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing.
abstract: During ageing, immobilization periods increase and are partially responsible of sarcopaenia by inducing a muscle atrophy which is hardly recovered from. Immobilization-induced atrophy is due to an increase of muscle apoptotic and proteolytic processes and decreased protein synthesis. Moreover, previous data suggested that the lack of muscle mass recovery might be due to a defect in protein synthesis response during rehabilitation. This study was conducted to explore protein synthesis during reloading and leucine supplementation effect as a nutritional strategy for muscle recovery. Old rats (22–24 months old) were subjected to unilateral hindlimb casting for 8 days (I8) and allowed to recover for 10–40 days (R10–R40). They were fed a casein (±leucine) diet during the recovery. Immobilized gastrocnemius muscles atrophied by 20%, and did not recover even at R40. Amount of polyubiquitinated conjugates and chymotrypsin- and trypsin-like activities of the 26S proteasome increased. These changes paralleled an ‘anabolic resistance' of the protein synthesis at the postprandial state (decrease of protein synthesis, P-S6 and P-4E-BP1). During the recovery, proteasome activities remained elevated until R10 before complete normalization and protein synthesis was slightly increased. With free leucine supplementation during recovery, if proteasome activities were normalized earlier and protein synthesis was higher during the whole recovery, it nevertheless failed in muscle mass gain. This discrepancy could be due to a ‘desynchronization' between the leucine signal and the availability of amino acids coming from casein digestion. Thus, when supplemented with leucine-rich proteins (i.e. whey) and high protein diets, animals partially recovered the muscle mass loss.
authors.affiliation: Clermont Université, Université d’Auvergne,Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Magne
authors.forename: Isabelle
authors.initials: I
authors.lastname: Savary-Auzeloux
authors.forename: Carole
authors.initials: C
authors.lastname: Migné
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Peyron
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
authors.forename: Didier
authors.initials: D
authors.lastname: Rémond
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
mesh_terms: D000375:Aging / Q000502:physiology*; D000596:Amino Acids / Q000097:blood; D000818:Animals; D004032:Diet; D019587:Dietary Supplements; D019417:Hindlimb Suspension / Q000379:methods; D007930:Leucine / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008894:Milk Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D009124:Muscle Proteins / Q000008:administration & dosage* / Q000378:metabolism; D009133:Muscular Atrophy / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D025801:Ubiquitin / Q000378:metabolism; D000067816:Whey Proteins
chemical_list: D000596:Amino Acids; D008894:Milk Proteins; D009124:Muscle Proteins; D025801:Ubiquitin; D000067816:Whey Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D007930:Leucine