title: Amino acids, independent of insulin, attenuate skeletal muscle autophagy in neonatal pigs during endotoxemia.
abstract: Sepsis induces loss of skeletal muscle mass by activating the ubiquitin proteasome (UPS) and autophagy systems. Although muscle protein synthesis in healthy neonatal piglets is responsive to amino acids (AA) stimulation, it is not known if AA can prevent the activation of muscle protein degradation induced by sepsis. We hypothesize that AA attenuate the sepsis-induced activation of UPS and autophagy in neonates.
  
  
  
  Newborn pigs were infused for 8 h with liposaccharide (LPS) (0 and 10 μg·kg(-1)·h(-1)), while circulating glucose and insulin were maintained at fasting levels; circulating AA were clamped at fasting or fed levels. Markers of protein degradation and AA transporters in longissimus dorsi (LD) were examined.
  
  
  
  Fasting AA increased muscle microtubule-associated protein light 1 chain 3 II (LC3-II) abundance in LPS compared to control, while fed AA levels decreased LC3-II abundance in both LPS and controls. There was no effect of AA supplementation on activated protein kinase (AMP), forkhead box O1 and O4 phosphorylation, nor on sodium-coupled neutral AA transporter 2 and light chain AA transporter 1, muscle RING-finger protein-1 and muscle Atrophy F-Box/Atrogin-1 abundance.
  
  
  
  These findings suggest that supplementation of AA antagonize autophagy signal activation in skeletal muscle of neonates during endotoxemia.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Adriana
authors.initials: A
authors.lastname: Hernandez-García
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Manjarín
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Agus
authors.initials: A
authors.lastname: Suryawan
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Hanh V
authors.initials: HV
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Renán A
authors.initials: RA
authors.lastname: Orellana
mesh_terms: D000596:Amino Acids / Q000097:blood*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D018805:Sepsis / Q000503:physiopathology; D034421:Sus scrofa; D013552:Swine; D013696:Temperature
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D007328:Insulin; D046988:Proteasome Endopeptidase Complex