title: Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model.
abstract: Supplementation of branched-chain amino acids (BCAA) has been demonstrated to promote skeletal muscle mass gain, but the mechanisms underlying this observation are still unknown. Since the regulation of muscle mass depends on a dynamic equilibrium (fasted losses-fed gains) in protein turnover, the aim of this study was to investigate the effects of BCAA supplementation on muscle protein synthesis and degradation in fed/fasted states and the related mechanisms. Fourteen 26- (Experiment 1) and 28-day-old (Experiment 2) piglets were fed reduced-protein diets without or with supplemental BCAA. After a four-week acclimation period, skeletal muscle mass and components of anabolic and catabolic signaling in muscle samples after overnight fasting were determined in Experiment 1. Pigs in Experiment 2 were implanted with carotid arterial, jugular venous, femoral arterial and venous catheters, and fed once hourly along with the intravenous infusion of NaH13CO₃ for 2 h, followed by a 6-h infusion of [1-13C]leucine. Muscle leucine kinetics were measured using arteriovenous difference technique. The mass of most muscles was increased by BCAA supplementation. During feeding, BCAA supplementation increased leucine uptake, protein synthesis, protein degradation and net transamination. The greater increase in protein synthesis than in protein degradation resulted in elevated protein deposition. Protein synthesis was strongly and positively correlated with the intramuscular net production of α-ketoisocaproate (KIC) and protein degradation. Moreover, BCAA supplementation enhanced the fasted-state phosphorylation of protein translation initiation factors and inhibited the protein-degradation signaling of ubiquitin-proteasome and autophagy-lysosome systems. In conclusion, supplementation of BCAA to reduced-protein diet increases fed-state protein synthesis and inhibits fasted-state protein degradation, both of which could contribute to the elevation of skeletal muscle mass in piglets. The effect of BCAA supplementation on muscle protein synthesis is associated with the increase in protein degradation and KIC production in the fed state.
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. zhenglf2013@webmail.hzau.edu.cn.
authors.forename: Liufeng
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. weihongkui@mail.hzau.edu.cn.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. weihongkui@mail.hzau.edu.cn.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100094, China. hepingli@cau.edu.cn.
authors.forename: Pingli
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Feed Science, Wuhan Polytechnic University, Wuhan 430023, China. zhaoShengjun1974@163.com.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. xiangquanhang@webmail.hzau.edu.cn.
authors.forename: Quanhang
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. pjm@webmail.hzau.edu.cn.
authors.forename: Jiaman
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. pengjian@mail.hzau.edu.cn.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. pengjian@mail.hzau.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D018753:Diet, Protein-Restricted; D019587:Dietary Supplements; D005215:Fasting; D007328:Insulin / Q000097:blood; D007651:Keto Acids / Q000097:blood; D007930:Leucine / Q000097:blood; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D013552:Swine; D010130:p-Aminohippuric Acid / Q000097:blood
chemical_list: D000597:Amino Acids, Branched-Chain; D007328:Insulin; D007651:Keto Acids; D009124:Muscle Proteins; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D010130:p-Aminohippuric Acid
keywords: branched-chain amino acids; muscle protein degradation; muscle protein synthesis; piglets; α-ketoisocaproate