title: Endotoxemia reduces skeletal muscle protein synthesis in neonates.
abstract: Protein synthesis in skeletal muscle is reduced by as much as 50% as early as 4 h after a septic challenge in adults. However, the effect of sepsis on muscle protein synthesis has not been determined in neonates, a highly anabolic population whose muscle protein synthesis rates are elevated and uniquely sensitive to insulin and amino acid stimulation. Neonatal piglets (n = 10/group) were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 microg. kg(-1). h(-1)]. Plasma amino acid and glucose concentrations were kept at the fed level by infusion of dextrose and a balanced amino acid mixture. Fractional protein synthesis rates were determined by use of a flooding dose of [(3)H]phenylalanine. LPS infusion produced a septic-like state, as indicated by an early and sustained elevation in body temperature, heart rate, and plasma tumor necrosis factor-alpha, interleukin-1, cortisol, and lactate concentrations. Plasma levels of insulin increased, whereas glucose and amino acids decreased, suggesting the absence of insulin resistance. LPS significantly reduced protein synthesis in longissimus dorsi muscle by only 11% and in gastrocnemius by only 15%, but it had no significant effect in masseter and cardiac muscles. LPS increased protein synthesis in the liver (22%), spleen (28%), kidney (53%), jejunum (19%), diaphragm (21%), lung (50%), and skin (13%), but not in the stomach, pancreas, or brain. These findings suggest that, when substrate supply is maintained, skeletal muscle protein synthesis in neonates compared with adults is relatively resistant to the catabolic effects of sepsis.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center and Sections of Critical Care and Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Renan A
authors.initials: RA
authors.lastname: Orellana
authors.forename: Pamela M J
authors.initials: PM
authors.lastname: O'Connor
authors.forename: Hanh V
authors.initials: HV
authors.lastname: Nguyen
authors.forename: Jill A
authors.initials: JA
authors.lastname: Bush
authors.forename: Agus
authors.initials: A
authors.lastname: Suryawan
authors.forename: M Carole
authors.initials: MC
authors.lastname: Thivierge
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Davis
mesh_terms: D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D019446:Endotoxemia / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011247:Pregnancy; D012270:Ribosomes / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007328:Insulin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D014409:Tumor Necrosis Factor-alpha