Leucine and α-Ketoisocaproic Acid, but Not Norleucine, Stimulate Skeletal Muscle Protein Synthesis in Neonatal Pigs , ,

Abstract

The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are not able to stimulate protein synthesis when raised in plasma to levels within the postprandial range. In this study, we evaluated the effect of leucine, alpha-ketoisocaproic acid (KIC), and norleucine infusion (0 or 400 micromol kg(-1) h(-1) for 60 min) on protein synthesis and activation of translation initiation factors in piglets. Infusion of leucine, KIC, and norleucine raised plasma levels of each compound compared with controls. KIC also increased (P < 0.01) and norleucine reduced (P < 0.02) plasma levels of leucine compared with controls. Administration of leucine and KIC resulted in greater (P < 0.006) phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) and eIF4G, lower (P < 0.04) abundance of the inactive 4E-BP1.eIF4E complex, and greater (P < 0.05) active eIF4G.eIF4E complex formation in skeletal muscle compared with controls. Protein synthesis in skeletal muscle was greater (P < 0.02) in leucine- and KIC-infused pigs than in those in the control group. Norleucine infusion did not affect muscle protein synthesis or translation initiation factor activation. In liver, neither protein synthesis nor activation of translation initiation factors was affected by treatment. These results suggest that the ability of leucine to act as a nutrient signal to stimulate skeletal muscle protein synthesis is specific for leucine and/or its metabolite, KIC.

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

“…Our results suggest that administration of leucine pulses increased translation initiation by inducing the phosphorylation of 4E-BP1 and S6K1 as well as the association of the eIF4E·eIF4G active complex. These results are consistent with previous findings in piglets administered leucine parenterally and enterally (8,34,36,59,74,77,85,86). For comparison we also measured eIF4E·eIF4G complex abundance in other tissues and found that leucine administration increased eIF4E·eIF4G complex formation in gastrocnemius and soleus muscles but not in heart, liver, or kidney.…”

Conversion of leucine to β-hydroxy-β-methylbutyrate by α-keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes

“…Among them, leucine is the most effective amino acid in stimulating protein synthesis through a direct activation of mTOR. Phosphorylation of mTOR drives to a 4E‐BP1 activation and an induction of S6K1 signalling 6, 10, 11, 12. Most studies on the beneficial effects of leucine enhancing protein synthesis have been carried out on leucine deficient media6, 7, 13 in in vitro studies or in models of muscle atrophy such as immobilization14 or experimental cachexia15, 16 involving a limited food intake period.…”

Competitive Edge: Review of the Role of Glutamine, Arginine and β -Hydroxy- β -Methylbutyrate Supplements for Enhancing Athletic Performance in Addition to Benefiting the Body During Times of Stress, Illness and Wound Healing

“…Though more studies are needed, from existing studies we can conclude that there is a potential role for combined supplementation of glutamine, arginine, and HMB in adequate doses to promote lean body mass and exercise performance [18,[20][21][22][23][24][25][26][27][28][29].…”

“…During athletic training, damage to the muscles results in the breakdown of leucine as well as increased HMB levels. Evidence suggests that taking HMB supplements might facilitate the body to slow down the destruction of muscle tissue [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Therefore, HMB has been studied as a sports performance supplement for enhancing strength and muscle mass.…”