Excess Leucine Intake Enhances Muscle Anabolic Signaling but Not Net Protein Anabolism in Young Men and Women

Abstract

Essential amino acids (EAA) stimulate skeletal muscle protein synthesis (MPS) in humans. Leucine may have a greater stimulatory effect on MPS than other EAA and/or decrease muscle protein breakdown (MPB). To determine the effect of 2 different leucine concentrations on muscle protein turnover and associated signaling, young men (n = 6) and women (n = 8) ingested 10 g EAA in 1 of 2 groups: composition typical of high quality proteins (CTRL; 1.8 g leucine) or increased leucine concentration (LEU; 3.5 g leucine). Participants were studied for 180 min postingestion. Fractional synthetic rate and leg phenylalanine and leucine kinetics were assessed on muscle biopsies using stable isotopic techniques. Signaling was determined by immunoblotting. Arterial leucine concentration and delivery to the leg increased in both groups and was significantly higher in LEU than in CTRL; however, transport into the muscle and intracellular availability did not differ between groups. MPS increased similarly in both groups 60 min postingestion. MPB decreased at 60 min only in LEU, but net muscle protein balance improved similarly. Components of mammalian target of rapamycin (mTOR) signaling were improved in LEU, but no changes were observed in ubiquitin-proteasome system signaling. Changes in light chain 3 and mTOR association with Unc-51-like kinase 1 indicate autophagy decreased more in LEU. We conclude that in 10 g of EAA, the leucine content typical of high quality proteins (~1.8 g) is sufficient to induce a maximal skeletal muscle protein anabolic response in young adults, but leucine may play a role in autophagy regulation.

Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females

“…When leucine-enriched supplements have been given to young subjects in connection with resistance exercise, little or no additional effect on protein synthesis or protein balance occurred (Katsanos et al 2006;Koopman et al 2005;Tipton et al 2009;Glynn et al 2010b). This lack of effect may, however, simply be due to the fact that the unenriched supplement itself already contains sufficient leucine to stimulate protein synthesis maximally.…”

Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

“…It has been reported that leucine deprivation in myoblast and myotubes increased (78) and leucine administration in cell culture (44,66), rats (87,88), and humans (29,41) decreased the phosphorylation of eEF2, a key component of the elongation process. In the current study, phosphorylation of eEF2 did not differ between the CON ϩ LEU and the CON ϩ ALA groups.…”

REDD2 expression in rat skeletal muscle correlates with nutrient-induced activation of mTORC1: responses to aging, immobilization, and remobilization

“…However, ingesting larger quantities of amino acids (e.g., 25-30 g) effectively stimulates muscle protein synthesis in both young and older individuals (55,56). Notably, the responsiveness of muscle protein synthesis in the elderly to small quantities of essential amino acids can be overcome by increasing the leucine content of the mixture (21,32). Similar results have been reported for studies in rats in which the age-related resistance of skeletal muscle protein synthesis to stimulation by a protein diet can be overcome by supplementation with leucine (14).…”