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Updated: Jun 19, 2026
06:47
Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Bile acid transport in hypercholesterolemic resistant rabbits
N N Izzat1, M Overturf, N W Weisbrodt
1Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, USA.
Summary
Altered bile acid transport, specifically reduced taurocholate uptake and increased apical sodium-dependent bile acid transporter (ASBT) mRNA in cholesterol-fed rabbits, contributes to hypercholesterolemia resistance. A specific ASBT polymorphism (P333L) further impairs bile acid transport.
Area of Science:
- Gastroenterology and Hepatology
- Molecular Biology
- Metabolic Diseases
Background:
- Hypercholesterolemia is a significant risk factor for cardiovascular disease.
- Bile acid metabolism plays a crucial role in cholesterol homeostasis.
- The apical sodium-dependent bile acid transporter (ASBT) is key for intestinal bile acid reabsorption.
Purpose of the Study:
- To investigate the role of bile acid transport and ASBT expression in a hypercholesterolemia-resistant rabbit model (CRT/mlo).
- To determine if altered bile acid excretion contributes to the resistant phenotype.
Main Methods:
- Examined taurocholate transport in ileal preparations of normal (NR) and CRT/mlo rabbits under regular and cholesterol-enriched diets.
- Quantified ASBT mRNA expression in response to dietary changes.
- Assessed the functional impact of an identified ASBT polymorphism (P333L) in transfected HEK293 cells.
Main Results:
- Cholesterol-enriched diet significantly reduced taurocholate transport in CRT/mlo rabbits but not NR rabbits.
- ASBT mRNA levels increased in cholesterol-fed CRT/mlo rabbits.
- A P333L ASBT polymorphism, found in CRT/mlo rabbits, significantly reduced taurocholate transport in vitro.
Conclusions:
- The hypercholesterolemia-resistant phenotype in CRT/mlo rabbits is associated with altered bile acid transport and metabolism.
- Changes in ASBT expression and function, including the P333L polymorphism, likely contribute to this phenotype.
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