Leucine Attenuates the Endotoxin‐induced Reduction in Skeletal Muscle Protein Synthesis in Neonatal Pigs

Abstract

Sepsis decreases protein synthesis (PS) in skeletal muscle and mitigates the anabolic response to Leucine (Leu) in mature animals. To determine if supplemental Leu can stimulate muscle PS in the neonate during endotoxemia, overnight fasted neonatal pigs were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic substrate clamps. Leu or saline was infused during the last h. PS and translation initiation factor activation were determined in skeletal muscle. LPS decreased protein synthesis by 36% in longissimus dorsi (LD), 28% in gastrocnemius (Gast) and 38% in soleus muscles compared to controls, but Leu infusion in the LPS group increased protein synthesis by 84% in LD, 81% in Gast and 83% in soleus compared to LPS infusion alone. Leu infusion alone compared to controls also increased protein synthesis in the LD, Gast and Soleus muscles. Leu infusion in both healthy and endotoxemic piglets compared to non-Leu infused piglets increased 4EBP1 and S6K1 phosphorylation and eIF4E·eIF4G complex formation in all muscles. These findings suggest that Leu supplementation can attenuate the reduction in muscle PS induced by endotoxemia by stimulating mTORC1-dependent translation in the neonate. (Supported by NIH AR444474, USDA/ARS 6250-51000-055, NIH HD072891, and USDA NIFA 2013-67015-20438)