Premium
Leucine Antagonizes Protein Degradation Induced by Endotoxin in Skeletal Muscle of Neonatal Pigs
Author(s) -
HernandezGarcia Adriana,
Orellana Renan,
Suryawan Agus,
Columbus Daniel,
Manjarin Rodrigo,
Nguyen Hanh,
Davis Teresa
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.755.3
Subject(s) - protein degradation , skeletal muscle , medicine , endocrinology , leucine , chemistry , anabolism , autophagy , ampk , amino acid , catabolism , ubiquitin , protein turnover , phosphorylation , protein biosynthesis , biology , biochemistry , metabolism , apoptosis , protein kinase a , gene
In neonatal animals, protein synthesis and degradation rates are high. Administration of the branched‐chain amino acid, leucine (Leu), stimulates muscle protein synthesis in neonatal pigs but less is known of the effects of Leu on protein degradation. Sepsis increases protein degradation (PD) in skeletal muscle but the effects of Leu on PD during a septic insult in the neonate are unknown. To determine if supplemental Leu can decrease muscle PD 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 was infused or not during the last h. Degradation signal activation was determined in longissimus dorsi (LD) muscle. LPS increased MuRF1 abundance and the LC3II/Total LC3 ratio, but did not have an effect on Atrogin‐1 abundance or AMPK phosphorylation. Although Leu had no effect on protein degradation markers in the healthy neonate, Leu reduced AMPK phosphorylation, MuRF1 abundance, and the LC3II/Total LC3 ratio but had no effect on Atrogin‐1 in pigs infused with LPS. Whole body AA utilization rates were increased by LPS but were not affected by Leu. These findings suggest that the anabolic effects of Leu antagonize the skeletal muscle protein loss induced by LPS in neonatal pigs by blunting the endoxemia‐induced activation of the ubiquitin‐proteasome and autophagy systems. (Supported by NIH AR444474, USDA/ARS 6250‐51000‐055,NIH HD072891, and USDA NIFA 2013‐67015‐20438)