354 - Hepatic Bile Acid Metabolism in Neonatal Rats Exposed to Phytosterols in Lipid Emulsions

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 354
Publication Number: 354.134

Rebekah J. Muthalaly, Atlantic Health System, Newark, NJ, United States; Elizabeth Eckman, MidAtlantic Neonatology Associates and BRInj, Cedar Knolls, NJ, United States; Chris Lee, Biomedical Research Institute of NJ, Cedar Knolls, NJ, United States; Aimee Herdt, Foundation for Morristown Medical Center and MidAtlantic Neonatology Associates, Morristown, NJ, United States; Naureen Memon, Goryeb Children's Hospital, Atlantic Health System, Morristown, NJ, United States

Presenting Author(s)

Rebekah J. Muthalaly, DO (she/her/hers)

Resident Physician
Atlantic Health System
Newark, New Jersey, United States

Background: Traditional lipid emulsions (LE) are derived from soybean oil and contain high concentrations of ω6 fatty acids (FA) and plant cholesterols, known as phytosterols (PS). Fish-oil (FO) containing LE contains high concentrations ω3 FA and lower concentrations of P</span>S. Animal and human studies have repeatedly shown that FO containing LE is hepatoprotective; whether this protection is due to the altered FA profile, a decrease in PS concentration, or a combination thereof is currently unknown. Using a novel phytosterolemia rat model, we studied the isolated effects of PS exposure on bile acid (BA) metabolism.

Objective:

To characterize hepatic BA concentrations and hepatic gene expression of key BA synthetic enzymes and transporters in rat pups exposed to PS.

Design/Methods: β-sitosterol, campesterol, and stigmasterol were dissolved in 2-hydroxypropyl-β-cyclodextrin (vehicle) to create a PS solution. Sprague-Dawley rat pups received daily intraperitoneal injections of PS solution from P0-P13 at a dose approximating PS content in 2 g/kg/d Intralipid (n=11), following which they were euthanized, and livers were extracted. Vehicle-exposed pups (n=11) and saline-injected pups (n=4) served as controls. Total BA in saline extracts of liver were quantified using an enzymatic colorimetric assay (GenWay). Expression of BA synthetic genes (Cyp7a1 and Cyp8b1) and transporters (Bsep, Mrp2, Abcg5/8) were measured using custom QuantiGene assays (ThermoFisher) and normalized to SDHA expression. Results were compared by ANOVA; differences between groups were considered significant if p< 0.05. Pearson correlation was used to examine relationships between BA levels and hepatic gene expression.

Results: Median levels of soluble hepatic BA were 14% higher in PS-exposed pups than in saline controls, but there were no statistically significant differences among the 3 groups (Fig 1). Similarly, no significant differences in the hepatic expression of selected genes were detected in PS-exposed pups. Hepatic BA content was negatively correlated with the expression level of BA synthetic genes Cyp7a1 (p=0.022) and Cyp8b1 (p=0.015) and positively correlated with sterol transporter Abcg5 (p=0.031).

Conclusion(s): PS exposure resulted in an increased trend towards hepatic BA accumulation; statistical significance was not reached most likely secondary to interindividual variation and small sample size. The relationship between hepatic BA content and gene expression of BA synthetic enzymes and sterol transporter reflects homeostatic mechanisms that prevent BA accumulation in the liver.