Dietary Leucine Supplementation Alters Muscle and Liver Protein Synthesis during Immune System Stimulation in Pigs
Authors: Rudar Marko , Huber Lee‐Anne , Zhu Cuilan L , de Lange Cornelis FM 
Published: November 2023

IntroductionImmune system stimulation (ISS) adversely affects protein and amino acid (AA) metabolism, leading to a decrease in skeletal muscle protein synthesis and increases in muscle protein degradation and visceral protein synthesis. While such short‐term changes in protein metabolism are beneficial for supporting an immune response, prolonged alterations are undesirable as it negatively affects whole‐body protein deposition (PD) and body weight gain. Among essential AA, Leu has a regulatory role in protein turnover in skeletal muscle and other tissues through its effect on the mechanistic target of rapamycin complex 1 signalling pathway. However, ISS may produce a short‐term resistance to Leu in skeletal muscle that impairs the anabolic effects of this AA.ObjectiveThe objective of this study was to evaluate the effects of ISS and dietary Leu supplementation on plasma AA and urea concentrations, and protein synthesis of various tissues during ISS.MethodsYorkshire pigs (initial body weight [BW] = 10.6 ± 1.1 kg) were surgically fitted with indwelling jugular vein catheters and assigned to one of three diets: 1. CON, 1.36% standardized ileal digestible (SID) Leu; 2. LEU‐M, 2.04% SID Leu; and 3. LEU‐H, 2.72% SID Leu. Immune system stimulation was induced in all LEU‐M and LEU‐H pigs and half of CON pigs with lipopolysaccharide (ISS+; n = 7, 8, and 7 for CON, LEU‐M, and LEU‐H, respectively); the remaining CON pigs were administered saline (ISS‐; n = 6). During ISS, feed allowance of ISS− and ISS+ pigs was equivalent. Blood was collected every 12 h at 0, 12, 24, and 36‐h after ISS was induced for determining plasma AA and urea concentrations. At 36 h, FSR of liver, plasma, gastrocnemius, and longissimus dorsi (LD) proteins were determined with a flooding dose of L‐[ring‐2H5]‐Phe.ResultsWhole‐body PD was decreased in ISS+ pigs (P < 0.01). Plasma AA and urea concentrations in ISS− pigs were constant over time, whereas they were increased in ISS+ pigs 12 h after ISS despite similar AA intake between ISS− and ISS+ pigs (P < 0.05). Plasma AA and urea concentrations at 36 h were similar between ISS− and ISS+ pigs except Phe (P = 0.053) and Thr (P = 0.054), which tended to decrease in ISS− pigs, and Gln (P = 0.072), which tended to increase in ISS+ pigs. Although dietary Leu supplementation increased plasma Leu concentration prior to ISS (Linear; P < 0.01), there was no linear effect at 36 h in ISS+ pigs. Dietary Leu supplementation decreased plasma Gln, Ile, and Val and urea concentrations at 36 h in ISS+ pigs (Linear; P < 0.05). Liver protein FSR was increased in ISS+ pigs (P < 0.05), whereas plasma and skeletal muscle protein FSR was not affected by ISS. Dietary Leu supplementation tended to decrease liver protein FSR (Linear; P = 0.052) and increase gastrocnemius protein FSR (Linear; P = 0.085) in ISS+ pigs, but there was no linear effect on LD protein FSR.ConclusionsIn this study, ISS resulted in acute increases in plasma AA and urea concentrations that reflect changes in tissue AA and protein metabolism. Skeletal muscle anabolic resistance to Leu was likely transient since protein synthesis rates were not reduced in gastrocnemius and LD muscles after ISS. However, the reduction in liver protein synthesis and increase in gastrocnemius protein synthesis in response to dietary Leu supplementation may facilitate AA partitioning for muscle PD during ISS.Support or Funding InformationNSERC 400994, OMAFRA 030087