|NG, KENNETH - Baylor College Of Medicine|
|STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)|
|SAENZ DE PIPAON, MIGUEL - Children'S Nutrition Research Center (CNRC)|
|OLUTOYE, OLUYINKA - Baylor College Of Medicine|
|Burrin, Douglas - Doug|
Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 5/28/2014
Publication Date: 6/9/2014
Citation: Ng, K., Stoll, B., Saenz De Pipaon, M., Olutoye, O., Burrin, D.G. 2014. Vitamin E added to intralipid and enriched in omegaven protects against PNALD in TPN-fed preterm pigs [abstract]. Journal of Pediatric Gastroenterology and Nutrition. 58(Suppl. 1)SP-N-0106:113.
Technical Abstract: Prolonged parenteral nutrition (PN) may lead to cholestasis and parenteral nutrition associated liver disease (PNALD). The etiology of PNALD is unknown, but plant phytosterols in soybean oil emulsions (e.g., Intralipid) have been suggested to negatively impact bile acid homeostasis (BAH) by antagonizing the bile acid sensing farnesoid X receptor (FXR). The fish oil emulsion Omegaven, abundant in vitamin E and docosahexaenoic acid (DHA) yet devoid of phytosterols, may positively impact the nuclear receptors pregnane X (PXR) and peroxisome proliferator-activated receptor-alpha (PPARalpha) receptors. We investigated the serum and hepatic tissue bile acid, serum biomarkers of liver injury, as well as target genes involved in BAH and fatty acid metabolism in TPN-fed preterm pigs given 4 different lipid emulsions. Preterm pigs were assigned to receive 14 days of either: 1) TPN + Intralipid (100% soybean oil)(IL); 2) TPN + Intralipid + Vitamin E (ILE); 3) TPN + Omegaven (100% fish oil)(OV); or 4) TPN + Omegaven + Phytosterols (PS). The final vitamin E concentration in the ILE group equaled the concentration in Omegaven. The three principal phytosterols found in Intralipid (campesterol, Beta-sitosterol, and stigmasterol) were added to Omegaven in the PS group. Serum levels of direct bilirubin, ALT, GGT, triglyceride, LDL, and hepatic triglyceride content were significantly lower (P<0.05) in the ILE, OV, and PS compared to IL pigs. CYP7A1 expression was lower (P<0.05) in the ILE, OV, and PS groups vs. IL. CYP3A29 and MRP2 expression were higher in ILE, OV, and PS groups vs. IL. OSTalpha (bile acid efflux transporter) expression was lower (P<0.05) in the ILE, OV, and PS groups vs. IL. BSEP (canalicular bile acid export) was slightly lower in the ILE, OV, and PS pigs vs. IL. CPT1A and CYP2E1 were higher in ILE, OV, and PS vs. IL pigs. Addition of phytosterols to Omegaven did not induce evidence of liver injury. The findings suggest that increased vitamin E and DHA are associated with up-regulated expression of PXR and PPARalpha downstream targets genes involved in bile acid and fatty acid metabolism and oxidation. These changes result in decreased bile acid synthesis and increased bile acid breakdown and canalicular bilirubin export; this triggered a compensatory down-regulation of the alternative bile acid export pathway (OSTalpha). Increased mitochondrial and microsomal fatty acid oxidation protects against hepatic triglyceride accumulation and steatosis. Vitamin E and DHA enriched in fish-oil emulsions protects hepatocytes via activation of bile acid and fatty acid metabolism. The beneficial effects of vitamin E in ILE group occurred despite the presence of abundant phytosterols.