title: Initiation factors for translation of proteins in the rectus abdominis muscle from patients on overnight standard parenteral nutrition before surgery.
abstract: Previous studies have provided conflicting conclusions concerning the efficacy of improving protein balance in patients by standard intravenous nutrition [TPN (total parenteral nutrition)], which is either explained by suboptimal nutritional regimens or insensitive clinical methods. The aim of the present study was therefore to evaluate the effects on the initiation of translation of skeletal muscle proteins by standard overnight TPN. A total of 12 patients who underwent standard surgery were included. TPN was provided as an all-in-one treatment by constant infusion [0.16 gN.kg(-1) of body weight.day(-1) (30 kcal.kg(-1) of body weight.day(-1))]. Saline-infused patients served as controls. Rectus abdominis muscle biopsies were taken at the time of the operation. The phosphorylation state of the proteins for initiation of translation was quantified. Plasma glucose, and serum insulin, glycerol, triacylglycerols (triglycerides) and NEFAs (non-esterified fatty acids; 'free fatty acids') were not significantly altered during TPN infusion, whereas total plasma amino acids increased, as shown by increases in methionine, phenylalanine, threonine, alanine, arginine, aspartic acid, glycine and histidine (P<0.05). Overnight TPN increased the formation of active eIF4G-eIF4E (where eIF is eukaryotic-initiation factor) complexes (P<0.05), whereas the inhibitory complex 4E-BP1 (eIF4E-binding protein)-eIF4E was moderately decreased (P<0.06). TPN increased the amount of the most phosphorylated form of 4E-BP1 (P<0.05), and increased the amount (P<0.04) and phosphorylation (P<0.01) of p70(S6K) (70 kDa ribosomal protein S6 kinase). In conclusion, an overnight pre-operative constant infusion of standard TPN altered initiation factor complexes, indicating activation of the initiation of protein translation in rectus abdominis muscle in the presence of increased plasma amino acid levels, but without a concomitant increase in energy substrates and insulin. In contrast with our results from previous studies, the methodology used in the present study appears to be more sensitive in reflecting directional changes in human muscle protein synthesis compared with traditional methods, particularly based on measurements of amino acid flux.
authors.affiliation: Department of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE413 45 Göteborg, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
authors.forename: Ulla
authors.initials: U
authors.lastname: Körner
authors.forename: Anders
authors.initials: A
authors.lastname: Hyltander
authors.forename: David
authors.initials: D
authors.lastname: Ljungman
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000378:metabolism; D000368:Aged; D000596:Amino Acids / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D039561:Eukaryotic Initiation Factor-4E / Q000032:analysis / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000601:surgery; D010288:Parenteral Nutrition; D010448:Peptide Initiation Factors / Q000032:analysis / Q000378:metabolism*; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017568:Rectus Abdominis / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000032:analysis / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D007328:Insulin; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C448959:ribosomal protein S6 kinase, 70kD, polypeptide 2