Depletion and Enrichment of Phytosterols in Soybean Oil Lipid Emulsions Directly Associate With Serum Markers of Cholestasis in Preterm Parenteral Nutrition-Fed Pigs

Authors

Greg Guthrie
Barbara Stoll
Shaji Chacko
Mahmoud Mohammad
Candace Style
Mariatu Verla
Oluyinka Olutoye
Deborah Schady
Charlotte Lauridsen
Nick Tataryn
Douglas Burrin

Publication Date

1-1-2022

Journal

Journal of Parenteral and Enteral Nutrition

DOI

10.1002/jpen.2088

PMID

33581699

PMCID

PMC8361868

PubMedCentral® Posted Date

1-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Biomarkers, Cholestasis, Emulsions, Fat Emulsions, Intravenous, Fish Oils, Humans, Parenteral Nutrition, Phytosterols, Soybean Oil, Swine, Soybean oil, phytosterols, total parenteral nutrition, bile salt export pump, bile acids, parenteral nutrition associated cholestasis

Abstract

Background: 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 soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets.

Methods: Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition (PN) prepared from a soybean oil-based emulsion containing either 24.0% (depleted [DEP]), 100% (Intralipid; normal phytosterol [NP] concentration), or 144% (enriched [ENR]) total phytosterol concentration.

Results: At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group, followed by NP and then DEP and ENT. Serum direct bilirubin, serum bile acids, and γ-glutamyltransferase were higher in the ENR and NP groups compared with 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.

Conclusion: The increase in serum direct bilirubin was lower in the DEP group vs the lipid emulsions with normal or ENR phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.