Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm PN-fed pigs

Authors: GUTHRIE, GREGORY - Children'S Nutrition Research Center (CNRC); STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC); MOHAMMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC); STYLE, CANDACE - Baylor College Of Medicine; VERLA, MARIATU - Baylor College Of Medicine; OLUTOYE, OLUYINKA - Baylor College Of Medicine; SCHADY, DEBORAH - Baylor College Of Medicine; LAURIDSEN, CHARLOTTE - Aarhuis University; TATARYN, NICHOLAS - Baylor College Of Medicine; Burrin, Douglas - Doug

Submitted to: Journal of Parenteral and Enteral Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2021
Publication Date: 2/13/2021
Citation: Guthrie, G., Stoll, B., Chacko, S., Mohammad, M., Style, C., Verla, M., Olutoye, O., Schady, D., Lauridsen, C., Tataryn, N., Burrin, D.G. 2021. Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm PN-fed pigs. Journal of Parenteral and Enteral Nutrition. https://doi.org/10.1002/jpen.2088.
DOI: https://doi.org/10.1002/jpen.2088

Interpretive Summary: Parenteral nutrition (PN) is a life-saving intervention for premature infants when oral feeding is not possible due to immature gut development. The long-term administration of PN contain pure soybean oil lipid emulsions is suggested as a contributing factor in the development of developing liver disease in these infants. Phytosterols are plant forms of cholesterol and these are especially enriched in soybean oil lipid emulsions. Phytosterols have been linked as a possible cause of liver disease where bile acids accumulate in the blood during PN. We performed a study in preterm neonatal PN fed pigs to test whether soybean lipid emulsions with different concentrations of phytosterols would affect the severity of liver disease after 3 weeks. Our results showed that higher phytosterol concentrations in PN lipid emulsions resulted in higher blood indices of liver disease and accumulation of phytosterols in liver tissue. Pigs given higher concentrations of lipid emulsion phytosterols did not show significant evidence of microscopic liver disease. Our results provide further evidence suggesting that phytosterols in parenteral lipid emulsions contribute to liver disease in infants.

Technical Abstract: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soy-based lipid emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets. Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition prepared from a soybean oil lipid emulsion containing either 24.0% (depleted, DEP), 100% (Intralipid, normal phytosterol concentration NP), and 144% (enriched, ENR) total phytosterol concentration. At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group followed by NP, then DEP and ENT. Serum direct bilirubin, serum bile acids, and gamma-glutamyltransferase was higher in the ENR and NP groups compared either DEP or ENT groups. All PN lipid groups showed evidence of mild hepatic steatosis, but no change in hepatic expression of proinflammatory cytokines or farnesoid X receptor target genes. The increase in serum direct bilirubin was lower in the depleted group vs. the lipid emulsions with normal or enriched phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.