Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats

Abstract

Background: Deficiency of choline, a required nutrient, is related to intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms.

Methods: Male Sprague-Dawley rats (4 weeks old) were fed AIN-93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites.

Results: The PN + choline group exhibited improved body weight compared with the PN group. PN impaired hepatic function, increased hepatic triglycerides, induced dyslipidemia, enhanced reactive oxygen species and malondialdehyde, and reduced total antioxidant capacity. The PN group had higher pathologic scores than the control group. These results were prevented by choline administration. Compared with the control group, PN increased PPARα promoter methylation and hepatic betaine concentration, reduced hepatic choline and phosphatidylcholine (PC) levels, decreased plasma choline and betaine concentrations, and downregulated PPARα and CPT1 mRNA and protein expression. Choline supplementation elevated hepatic choline and PC levels and enhanced plasma choline, betaine, and PC concentrations but reduced hepatic betaine level, reversed PPARα promoter hypermethylation, and upregulated PPARα and CPT1 mRNA and protein expression in PN-fed rats, compared with rats receiving PN alone.

Conclusion: Choline addition to PN may prevent IFALD by reducing oxidative stress, enhancing hepatic fat export, and promoting fatty acid catabolism in immature rats receiving PN.

Keywords: carnitine palmitoyltransferase 1; choline; intestinal failure-associated liver disease; methylation; peroxisomal proliferator-activated receptor alpha.