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Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats.
JPEN J Parenter Enteral Nutr. 2018 02; 42(2):436-445.JJ

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.

Authors+Show Affiliations

Department of Clinical Nutrition, School of Medicine, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China. Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Shanghai Institute of Pediatric Research, Shanghai, China.Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Department of Clinical Nutrition, School of Medicine, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China. Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Shanghai Institute of Pediatric Research, Shanghai, China.Department of Clinical Nutrition, School of Medicine, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China. Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.Department of Clinical Nutrition, School of Medicine, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, China. Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Shanghai Institute of Pediatric Research, Shanghai, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27856995

Citation

Zhu, Jie, et al. "Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats." JPEN. Journal of Parenteral and Enteral Nutrition, vol. 42, no. 2, 2018, pp. 436-445.
Zhu J, Lu T, Chen F, et al. Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats. JPEN J Parenter Enteral Nutr. 2018;42(2):436-445.
Zhu, J., Lu, T., Chen, F., Yan, J., Chen, F., Zhang, Q., Wang, J., Yan, W., Yu, T., Tang, Q., & Cai, W. (2018). Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats. JPEN. Journal of Parenteral and Enteral Nutrition, 42(2), 436-445. https://doi.org/10.1177/0148607116677048
Zhu J, et al. Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats. JPEN J Parenter Enteral Nutr. 2018;42(2):436-445. PubMed PMID: 27856995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Choline Protects Against Intestinal Failure-Associated Liver Disease in Parenteral Nutrition-Fed Immature Rats. AU - Zhu,Jie, AU - Lu,Ting, AU - Chen,Fei, AU - Yan,Junkai, AU - Chen,Fan, AU - Zhang,Qiaosen, AU - Wang,Jifan, AU - Yan,Weihui, AU - Yu,Tingxi, AU - Tang,Qingya, AU - Cai,Wei, Y1 - 2017/12/15/ PY - 2016/05/22/received PY - 2016/10/04/accepted PY - 2016/11/20/pubmed PY - 2019/12/4/medline PY - 2016/11/19/entrez KW - carnitine palmitoyltransferase 1 KW - choline KW - intestinal failure-associated liver disease KW - methylation KW - peroxisomal proliferator-activated receptor alpha SP - 436 EP - 445 JF - JPEN. Journal of parenteral and enteral nutrition JO - JPEN J Parenter Enteral Nutr VL - 42 IS - 2 N2 - 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. SN - 1941-2444 UR - https://www.unboundmedicine.com/medline/citation/27856995/Choline_Protects_Against_Intestinal_Failure_Associated_Liver_Disease_in_Parenteral_Nutrition_Fed_Immature_Rats_ L2 - https://doi.org/10.1177/0148607116677048 DB - PRIME DP - Unbound Medicine ER -