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

• Published in: The Journal of physiology 2012-04, Vol.590 (8), p.2035-2049
• Main Authors: Magne, Hugues, Savary‐Auzeloux, Isabelle, Migné, Carole, Peyron, Marie‐Agnès, Combaret, Lydie, Rémond, Didier, Dardevet, Dominique
• Format: Article
• Language: English
• Subjects: Aging - physiology; Amino Acids - blood; Animals; Diet; Dietary Supplements; Food and Nutrition; Hindlimb Suspension - methods; Integrative; Leucine - administration & dosage; Leucine - metabolism; Life Sciences; Male; Milk Proteins - metabolism; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - physiology; Muscle Proteins - administration & dosage; Muscle Proteins - metabolism; Muscular Atrophy - diet therapy; Muscular Atrophy - metabolism; Muscular Atrophy - physiopathology; Proteasome Endopeptidase Complex - metabolism; Rats; Rats, Wistar; Ubiquitin - metabolism; Whey Proteins
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2011.226266

Key points  •  During ageing, there is a lack of recovery of muscle mass following immobilization. •  We showed, in old rats, an ‘anabolic resistance’ of muscle protein synthesis to food intake during immobilization and only a slight increase of protein synthesis during the recovery, which explain a poor muscle nitrogen balance that is insufficient to induce a muscle mass gain. •  A supplementation with free leucine, an essential amino acid known to stimulate muscle protein metabolism, was efficient in inducing a greater anabolism but failed to induce muscle mass recovery. •  This discrepancy was explained by a ‘desynchronization’ between the leucine signal and amino acids coming from dietary protein digestion. •  An induction of a larger increase and a longer availability of amino acids in the postprandial state with rich‐protein leucine (i.e. whey) and high protein diets were efficient in inducing a muscle mass recovery after immobilization.   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 ‘desynchron