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Title: Lipid emulsions containing fish oil protect against PN-induced cholestatic liver disease in preterm piglets

item VLAARDINGERBROEK, HESTER - Erasmus Medical Center
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item BENIGHT, NANCY - Children'S Nutrition Research Center (CNRC)
item VAN GOUDOEVER, JOHANNES - Children'S Nutrition Research Center (CNRC)
item OLUTOYE, OLUYINKA - Children'S Nutrition Research Center (CNRC)
item Burrin, Douglas - Doug

Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 4/14/2011
Publication Date: 4/30/2011
Citation: Vlaardingerbroek, H., Stoll, B., Benight, N., Van Goudoever, J.B., Olutoye, O., Burrin, D.G. 2011. Lipid emulsions containing fish oil protect against PN-induced cholestatic liver disease in preterm piglets [abstract]. In: Proceedings of the 2011 Annual Conference of the Pediatric Academic Society and the Asian Society for Pediatric Research. Session: Neonatal fetal nutrition and metabolism II, April 30-May 3, 2011, Denver, Colorado. 3670.6.

Interpretive Summary:

Technical Abstract: During their first weeks of life preterm infants are dependent on parenteral nutrition (PN). However, PN is associated with the development of cholestasis (PN Associated Liver Disease PNALD). Studies in children showed that fish oil-based lipid emulsions can reverse PNALD; whether they prevent PNALD in preterm neonates is unknown. Mechanisms that can explain protective action of fish oil emulsions include 1) anti-inflammatory effects of n-3 fatty acids (FA), 2) limiting soybean oil, rich in n-6FAs and phytosterols, 3) reduced lipid load. The objective of this study was to test whether lipid emulsions with varying amounts of fish oil prevent the development of PNALD in preterm pigs. Preterm pigs bearing venous and arterial catheters were randomly assigned to 4 groups (7-14 pigs/group; equal daily macronutrient intake with 5 g/kg lipid): PN+soybean oil (100 percent) (Intralipid,IL), PN+fish oil (100 percent)(Omegaven,OV), PN+oil mixture w/soybean (30 percent)-coconut (30 percent)-olive (25 percent)-fish (15 percent) (SMOF); a reference group was fed milk formula enterally (EN). Serum AST, ALT, ALP, LDH, GGT, and bilirubin were measured at d 0, 7, and 14. At d 14 pigs were killed and liver histopathology, triglyceride (TG) content, and bile acid metabolism gene expression analyzed. The bilirubin and GGT levels were higher in IL vs EN piglet, whereas OV and SL treatments were lower than IL pigs. Liver TG was highest in IL pigs compared to all other and were similar in SL, OV and EN pigs. Liver weight was similar in all TPN groups and higher than EN pigs. Direct bilirubin and GGT increased markedly from d 0-14 in IL pigs, compared to other groups. Liver histopathology showed microvesicular steatosis and neutrophil infiltrate mainly in IL pigs. Compared to EN pigs, all PN treatments suppressed hepatic mRNA of FXR and its target genes BSEP (bile transporter) and (CYP7A1 bile acid synthesis). In conclusion, in preterm pigs, PN with soybean oil induced hepatic cholestasis and steatosis and this was largely prevented with either 100 percent or 15 percent fish oil emulsions. Fish oil did not prevent the PN-induced suppression of bile acid metabolism FXR target genes.