Abstract

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression.

Highlights

  • Parenteral nutrition (PN) is a life-saving treatment for infants and children who are unable to adequately absorb crucial nutrients due to intestinal failure [1,2,3]

  • The changes in several biochemical parameters that reflect hepatic function, which include Lipids droplets (LD) accumulation, endoplasmic reticulum (ER) and mitochondrial structures, and ER stress, were compared between primary newborn rabbit hepatocytes that were treated with two different oil-based lipid emulsions

  • Our results reveal that Soybean oil-based lipid emulsions (SOLE) caused significant damage to both the ER and mitochondria, resulting in LD accumulation, ER stress, and eventual hepatocyte malfunction

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Summary

Introduction

Parenteral nutrition (PN) is a life-saving treatment for infants and children who are unable to adequately absorb crucial nutrients due to intestinal failure [1,2,3]. Long-term PN administration can have severe deleterious health effects, such as promoting the development of life-threatening PN-associated liver disease (PNALD) [2]. PNALD is characterized by significant alterations to liver histology that range from hepatocyte steatosis and cholestasis to liver fibrosis, cirrhosis, or complete liver failure [2]. PNALD is a major cause of morbidity and mortality in infants requiring long-term PN, with ten deaths and one referral for liver transplantation in the first year of life among 66 PN-associated cholestasis patients (17%) [4].

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