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Title: New generation lipid emulsions prevent PNALD in chronic parentally fed preterm pigs

item VLAARDINGERBROEK, HESTER - Sophia Children'S Hospital
item NG, KENNETH - Children'S Nutrition Research Center (CNRC)
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item BENIGHT, NANCY - Children'S Nutrition Research Center (CNRC)
item CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC)
item KLUIJTMANS, LEO - Baylor College Of Medicine
item KULIK, WIM - Radboud University
item SQUIRES, E. JAMES - University Of Amsterdam
item OLUTOYE, OLUYINKA - Texas Children'S Hospital
item SCHADY, DEBORAH - Baylor College Of Medicine
item FINEGOLD, MILTON - Baylor College Of Medicine
item VAN GOUDOEVER, JOHANNES - Baylor College Of Medicine
item Burrin, Douglas - Doug

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2014
Publication Date: 1/29/2014
Citation: Vlaardingerbroek, H., Ng, K., Stoll, B., Benight, N., Chacko, S., Kluijtmans, L.A., Kulik, W., Squires, E., Olutoye, O., Schady, D., Finegold, M.L., Van Goudoever, J.B., Burrin, D.G. 2014. New generation lipid emulsions prevent PNALD in chronic parentally fed preterm pigs. Journal of Lipid Research. 55(3):466-477.

Interpretive Summary: Each year, more than half a million infants are born prematurely and have immature guts that cannot absorb enough food to sustain life. In order to nourish these babies, physicians use a life-saving therapy called total parenteral nutrition in which an emulsion of fluid containing electrolytes, glucose, amino acids, vitamins, minerals, and fats is infused intravenously. In the U.S., the only lipid emulsion approved for use in infants is based on soybean oil. Unfortunately, if babies remain on this emulsion for a long period, they develop parenteral nutrition-associated liver disease (PNALD), which can be life-threatening. New emulsions are approved in Europe and may provide a healthier alternative to soybean oil for premies. The current study tested two new lipid emulsions in premature, newborn piglets. One group received the soybean-oil based emulsion, while the others got either an emulsion based on pure fish oil or a mixture that contained soybean oil, medium chain triglycerides, and olive and fish oils. The result showed that the pigs on the two new emulsions – one containing pure fish oil and the other with 15% fish oil – were less likely to develop PNALD. The result demonstrate novel evidence that these new lipid emulsions can prevent PNALD when given at equal lipid loads.

Technical Abstract: Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fish oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14-day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7alpha-hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OSTalpha) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both OV and SL emulsions. Due to the presence of phytosterols in the SL emulsion, the differences in cholestasis and liver injury among lipid emulsion groups in vivo were weakly correlated with plasma and hepatic phytosterol content.