Cholestyramine alters bile acid amounts and the expression of cholesterol-related genes in rabbit intestinal and hepatic tissues
Abstract
Objective Cholestyramine (CHO), as a bile acid sequestering exchange resin, has been widely used to treat hypercholesterolemia. The aim of this study was to explore how CHO regulated serum cholesterol amounts and bile acid levels in animal models. Methods New Zealand White rabbits were randomly assigned to the control (given distilled water) and CHO-treated (given CHO solution 1 g/kg per day for 2 weeks) groups. To assess bile acid pool size, bile fistulas were constructed in five rabbits in each group. Serum cholesterol levels and biliary and fecal bile outputs were determined. Liver cholesterol 7α-hydroxylase ( CYP7A1 ), small heterodimer partner ( SHP ), bile salt export pump ( BSEP ), ileal bile acid-binding protein ( IBABP ) and LDL receptor ( LDL-R ) mRNA expressions were assessed by real-time polymerase chain reaction. CYP7A1 activity was also determined. Results CHO treatment decreased serum cholesterol levels by 12.1%. Although CHO did not change the bile acid pool size and biliary bile acid output, it significantly increased fecal bile acid output. Interestingly, CHO also significantly increased the expression and activity of CYP7A1, as well as IBABP and LDL-R mRNA expressions, but decreased hepatic SHP and BSEP gene expressions. Conclusion CHO markedly alters bile acid and cholesterol amounts in rabbit intestinal and liver tissues, downregulating genes responsible for cholesterol homeostasis.
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CHR-fed WT and CarKO mice exhibit elevated mRNA levels of BA synthesis genes and reduced expression of BA export and detoxification genes compared with chow-fed mice, to compensate for a reduced BA pool.
“To compensate for a reduced BA pool,5,39,40 we observed that CHR-fed WT and CarKO mice exhibited elevated mRNA levels of BA synthesis genes and reduced expression of BA export and detoxification genes compared with chow-fed mice (Figure 10A–C).”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [40]
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- Authors
- Qiu, D. N., Shang, Q., Sun, D. Y., Ding, W. Q., Luo, Z. G., Chen, J., Jiang, W. R., Huang, J. P., & Jiang, X. Y.
- Affiliations
- Fudan University (CN)
- VA New Jersey Health Care System (US)
- Department of Gastroenterology Huashan Hospital, Fudan University Shanghai China
- Corresponding author
- Ding, Wei Qun
- Venue
- Journal of Digestive Diseases
- Publisher
- Wiley
- Published
- 2017-02
- Volume
- 18
- Issue
- 2
- Pages
- 107-114
- ISSN
- 1751-2972 (ISSN-L)
- 1751-2980
- OpenAlex
- W2570175679
- Cited by
- 4
- References
- 32
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2020: 1
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Digestive Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shanghai Municipal Health Bureau Research Fund (2010Y057)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- cholestyramine, bile acid sequestrants, bile acid pool, serum cholesterol, cholesterol homeostasis, CYP7A1, small heterodimer partner, bile salt export pump, ileal bile acid binding protein, LDL receptor, intestinal gene expression, hepatic gene expression, hypercholesterolemia
- MeSH terms
- Animals, Anion Exchange Resins, Bile Acids and Salts, Cholesterol, Cholesterol 7-alpha-Hydroxylase, Cholestyramine Resin, Feces, Intestinal Mucosa, Liver, Male, Rabbits, Random Allocation, Receptors, LDL, RNA, Messenger, Gene Expression, Receptors, Cytoplasmic and Nuclear, ATP-Binding Cassette Transporters, Fatty Acid-Binding Proteins
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