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Title: Vitamin E in new-generation lipid emulsions protects against parenteral nutrition-associated liver disease in parenteral nutrition-fed preterm pigs

Author
item NG, KENNETH - Baylor College Of Medicine
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC)
item SAENZ DE PIPAON, MIGUEL - Children'S Nutrition Research Center (CNRC)
item LAURIDSEN, CHARLOTTE - Aarhus University
item GRAY, MATTHEW - University Of Guelph
item SQUIRES, E. JAMES - University Of Guelph
item MARINI, JUAN - Children'S Nutrition Research Center (CNRC)
item ZAMORA, IRVING - Baylor College Of Medicine
item OLUTOYE, OLUYINKA - Baylor College Of Medicine
item Burrin, Douglas - Doug

Submitted to: Journal of Parenteral and Enteral Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/13/2014
Publication Date: 1/16/2015
Citation: Ng, K., Stoll, B., Chacko, S., Saenz De Pipaon, M., Lauridsen, C., Gray, M., Squires, E., Marini, J.C., Zamora, I.J., Olutoye, O.O., Burrin, D.G. 2015. Vitamin E in new-generation lipid emulsions protects against parenteral nutrition-associated liver disease in parenteral nutrition-fed preterm pigs. Journal of Parenteral and Enteral Nutrition. DOI: 10.1177/0148607114567900.

Interpretive Summary: Many of the more than 500,000 infants born prematurely in the United States each year rely on intravenous nutrition support. In order to survive and grow, infants rely on the technique called Total Parenteral Nutrition (TPN) where they are fed intravenously with an emulsion of fluid, electrolytes, amino acids, glucose, fats, vitamins and minerals. The lipid component is especially important since it has been linked to parenteral nutrition-assisted liver disease (PNALD). Our previous studies showed that newly developed lipid emulsions prevent PNALD perhaps because of differences in the presence of vitamin E or absence of phytosterols, a plant form of cholesterol. Using premature, TPN-fed piglets as a model for human infants, we tested whether addition of vitamin E to the currently U.S. approved soybean lipid emulsion or phytosterols to a newly developed fish oil emulsion affected the risk for PNALD. We found that adding the vitamin E (alpha-tocopherol) to Intralipid prevented PNALD, but, surprisingly, adding phytosterols to Omegaven did not result in liver damage. These results challenge the idea that phytosterol cause PNALD and shows that vitamin E is protective and may explain the benefit of new generation emulsions.

Technical Abstract: Parenteral nutrition (PN) in preterm infants leads to PN-associated liver disease (PNALD). PNALD has been linked to serum accumulation of phytosterols that are abundant in plant oil but absent in fish oil emulsions. Whether modifying the phytosterol and vitamin E composition of soy and fish oil lipid emulsions affects development of PNALD in preterm pigs. We measured markers of PNALD in preterm pigs that received 14 days of PN that included 1 of the following: (1) Intralipid (IL, 100% soybean oil), (2) Intralipid + vitamin E (ILE, d-alpha-tocopherol), (3) Omegaven (OV, 100% fish oil), or (4) Omegaven + phytosterols (PS, beta-sitosterol, campesterol, and stigmasterol). Serum levels of direct bilirubin, gamma glutamyl transferase, serum triglyceride, low-density lipoprotein, and hepatic triglyceride content were significantly lower (P < .05) in the ILE, OV, and PS compared to IL. Hepatic cholesterol 7-hydroxylase and organic solute transporter-alpha expression was lower (P < .05) and portal plasma FGF19 higher in the ILE, OV, and PS vs IL. Hepatic expression of mitochondrial carnitine palmitoyltransferase 1A and microsomal cytochrome P450 2E1 fatty acid oxidation genes was higher in ILE, OV, and PS vs IL. In vivo (13)C-CDCA clearance and expression of pregnane X receptor target genes, cytochrome P450 3A29 and multidrug resistance-associated protein 2, were higher in ILE, OV, and PS vs IL. Alpha-tocopherol in Omegaven and added to Intralipid prevented serum and liver increases in biliary and lipidemic markers of PNALD in preterm piglets. The addition of phytosterols to Omegaven did not produce evidence of PNALD.