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Early Parenteral Nutrition Evokes a Phenotype of Autophagy Deficiency in Liver and Skeletal Muscle of Critically Ill Rabbits.
MedLine Citation:
PMID:  22396453     Owner:  NLM     Status:  Publisher    
Muscular and hepatic abnormalities observed in artificially fed critically ill patients strikingly resemble the phenotype of autophagy-deficient mice. Autophagy is the only pathway to clear damaged organelles and large ubiquitinated proteins and aggregates. Fasting is its strongest physiological trigger. Severity of autophagy deficiency in critically ill patients correlated with the amount of infused amino acids. We hypothesized that impaired autophagy in critically ill patients could partly be evoked by early provision of parenteral nutrition enriched with amino acids in clinically used amounts. In a randomized laboratory investigation, we compared the effect of isocaloric moderate-dose iv feeding with fasting during illness on the previously studied markers of autophagy deficiency in skeletal muscle and liver. Critically ill rabbits were allocated to fasting or to iv nutrition (220 kcal/d, 921 kJ/d) supplemented with 50 kcal/d (209 kJ/d) of either glucose, amino acids, or lipids, while maintaining normoglycemia, and were compared with healthy controls. Fasted critically ill rabbits revealed weight loss and activation of autophagy. Feeding abolished these responses, with most impact of amino acid-enriched nutrition. Accumulation of p62 and ubiquitinated proteins in muscle and liver, indicative of insufficient autophagy, occurred with parenteral feeding enriched with amino acids and lipids. In liver, this was accompanied by fewer autophagosomes, fewer intact mitochondria, suppressed respiratory chain activity, and an increase in markers of liver damage. In muscle, early parenteral nutrition enriched with amino acids or lipids aggravated vacuolization of myofibers. In conclusion, early parenteral nutrition during critical illness evoked a phenotype of autophagy deficiency in liver and skeletal muscle.
Sarah Derde; Ilse Vanhorebeek; Fabian Güiza; Inge Derese; Jan Gunst; Birthe Fahrenkrog; Wim Martinet; Hilke Vervenne; Eric-Jan Ververs; Lars Larsson; Greet Van den Berghe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-6
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department and Laboratory of Intensive Care Medicine (S.D., I.V., F.G., I.D., J.G., H.V., E.-J.V., G.V.d.B.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; Institute of Molecular Biology and Medicine (B.F.), Université Libre de Bruxelles, B-6041 Gosselies, Belgium; Division of Pharmacology (W.M.), University of Antwerp, B-2610 Antwerp, Belgium; and Department of Clinical Neurophysiology (L.L.), Uppsala University, SE-751 85, Sweden.
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