Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Dysregulation of bile acid homeostasis in parenteral nutrition mouse model.

Authors: Zhan, Le; Yang, Ill; Kong, Bo; Shen, Jianliang; Gorczyca, Ludwik; Memon, Naureen; Buckley, Brian T; Guo, Grace L

Published In Am J Physiol Gastrointest Liver Physiol, (2016 Jan 15)

Abstract: Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD.

PubMed ID: 26564717 Exiting the NIEHS site

MeSH Terms: Animals; Bile Acids and Salts/metabolism*; Body Weight/physiology; Cytochrome P-450 Enzyme System/genetics; Cytochrome P-450 Enzyme System/metabolism; Disease Models, Animal; Gene Expression Regulation*; Homeostasis/physiology*; Liver Diseases/genetics; Liver Diseases/metabolism; Liver X Receptors; Liver/metabolism*; Mice; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics; Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism; Orphan Nuclear Receptors/genetics; Orphan Nuclear Receptors/metabolism; Parenteral Nutrition*; RNA, Messenger/genetics; RNA, Messenger/metabolism

Back
to Top