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Mixed Lipid, Fish Oil, and Soybean Oil Parenteral Lipids Impact Cholestasis, Hepatic Phytosterol, and Lipid Composition

Isaac, Daniela Migliarese*; Alzaben, Abeer S.†,‡; Mazurak, Vera C.; Yap, Jason*; Wizzard, Pamela R.*; Nation, Patrick N.§; Zhao, Yuan-Yuan; Curtis, Jonathan M.; Sergi, Consolato§; Wales, Paul W.*,¶,||,#; Mager, Diana R.*,†; Turner, Justine M.*,†

Journal of Pediatric Gastroenterology and Nutrition: June 2019 - Volume 68 - Issue 6 - p 861–867
doi: 10.1097/MPG.0000000000002313
Original Articles: Nutrition
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Objectives: In parenteral nutrition-dependent infants and children, intestinal failure (IF)-associated liver disease (IFALD) remains an important problem. A comparative study was undertaken of parenteral mixed lipid (ML), ω-3 predominant fish oil (FO), and ω-6 predominant soybean oil (SO) emulsions in regards to hepatic phytosterol, neutral lipid, fatty acid (FA) content, and the relationship to cholestasis in piglets.

Methods: Neonatal piglets received parenteral nutrition, varying in lipid dose (5 or 10 g· kg−1 · day−1) and formulation: SO5 (n = 5), SO10 (n = 5), FO5 (n = 5), and ML10 (n = 5). On day 14, liver chemistry, bile flow, histology and neutral lipid staining were assessed. Hepatic triglyceride FA content was determined using thin layer and gas chromatography, and phytosterol content was assessed using gas chromatography-mass spectrometry.

Results: SO groups had higher prevalence of biochemical cholestasis (P < 0.04) and lower bile flow (P < 0.0001). Hepatic campesterol, stigmasterol, and β-sitosterol were highest in SO10 (P < 0.0001). Hepatic FA (P < 0.03) and ω-6/ω-3 FA ratio (P < 0.0001) were higher in the SO groups. Neutral lipid accumulation (P = 0.3) and liver histology (P = 0.16) were not different between groups. Univariate predictors of bile flow were: campesterol (r = −0.77, P = 0.001), β-sitosterol (r = −0.74, P = 0.002), stigmasterol (r = −0.74, P = 0.002), ω-6 FA (r = −0.72, P = 0.002), and ω-3 FA (r = 0.59, P = 0.02). Only campesterol independently predicted bile flow.

Conclusions: ML and FO lipid emulsions reduce cholestasis in association with lowered hepatic phytosterol and lipid content. Lower hepatic phytosterol and ω-6 FA content, and higher ω-3 FA content are hepatoprotective. Multivariate analysis suggests reduced phytosterol accumulation may best explain the hepatoprotective effect of fish oil-containing lipids.

*Department of Pediatric Gastroenterology and Nutrition

Department of Agricultural, Food and Nutritional Science, University of Alberta

Clinical Nutrition Program, Department of Health, The College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University

§Department of Laboratory Medicine and Pathology, University of Alberta, Alberta, Edmonton

Research Institute, Hospital for Sick Children

||Division of General Surgery, Hospital for Sick Children, University of Toronto

#Group for Improvement of Intestinal Function and Treatment, Hospital for Sick Children, Toronto, Ontario, Canada.

Address correspondence and reprint requests to Daniela Migliarese Isaac, MD, FRCPC, Pediatric Gastroenterology Subspecialty Resident, Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, 11405 87th Avenue NW, Edmonton, AB, Canada T6G 1C9 (e-mail: migliare@ualberta.ca).

Received 13 December, 2018

Accepted 12 February, 2019

Ethics Approval: Obtained from the Faculty of Agricultural, Life and Environmental Sciences Animal Policy and Welfare Committee at the University of Alberta (AUP00000153).

This study was supported by an operating grant from the Canadian Institutes of Health Research (ISO110834). Parenteral lipid was provided in kind by Fresenius Kabi. Abeer Alzaben and the lipidomics assessment was supported by the Saudi Cultural Bureau, Ministry of Education, Saudi Arabia. Funding sources were not involved in study design, the collection, analysis or interpretation of data; writing the manuscript, nor the decision to submit the article for publication.

This study was supported by Fresenius Kabi financially and with lipids in kind.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,