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: Gilbert Zeanandin, Michèle Balage, Stéphane M Schneider, Joëlle Dupont, Xavier Hébuterne, Isabelle Mothe-Satney, Dominique Dardevet
• Journal: Age (Dordrecht, Netherlands) (Age (Dordr)) Vol. 34 Issue 2 Pg. 371-87 (Apr 2012) ISSN: 1574-4647 [Electronic] Netherlands
• PMID: 21472380 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• RNA
• mTOR protein, rat
• Ribosomal Protein S6 Kinases
• Rps6kb1 protein, rat
• TOR Serine-Threonine Kinases
• Leucine
• Glucose

Topics

• Adipose Tissue (drug effects, metabolism)
• Aging (drug effects, physiology)
• Animals
• Biological Transport (genetics)
• Blotting, Western
• Dietary Supplements
• Disease Models, Animal
• Follow-Up Studies
• Glucose (metabolism)
• Glucose Tolerance Test
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Leucine (administration & dosage)
• Male
• Muscle, Skeletal (drug effects, metabolism)
• RNA (genetics)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Ribosomal Protein S6 Kinases (biosynthesis, drug effects, genetics)
• Sarcopenia (diet therapy, genetics, metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (biosynthesis, drug effects, genetics)
• Time Factors