
New Key Publication:Bile Acid Sequestration via Colesevelam Reduces Bile Acid Hydrophobicity and Improves Liver Pathology in Cyp2c70−/− Mice with a Human-like Bile Acid Composition
Abstract
Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70−/− (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with the development of liver fibrosis. The aim of this study was to determine whether BA sequestration modulates liver pathology in Western type-diet (WTD)-fed KO mice. The BA sequestrant colesevelam was mixed into the WTD (2% w/w) of male Cyp2c70+/+ (WT) and KO mice and the effects were evaluated after 3 weeks of treatment. Colesevelam increased fecal BA excretion in WT and KO mice and reduced the hydrophobicity of biliary BAs in KO mice. Colesevelam ameliorated diet-induced hepatic steatosis in WT mice, whereas KO mice were resistant to diet-induced steatosis and BA sequestration had no additional effects on liver fat content. Total cholesterol concentrations in livers of colesevelam-treated WT and KO mice were significantly lower than those of untreated controls. Of particular note, colesevelam treatment normalized plasma levels of liver damage markers in KO mice and markedly decreased hepatic mRNA levels of fibrogenesis-related genes in KO mice. Lastly, colesevelam did not affect glucose excursions and insulin sensitivity in WT or KO mice. Our data show that BA sequestration ameliorates liver pathology in Cyp2c70−/− mice with a human-like bile acid composition without affecting insulin sensitivity.
Authors:
- Anna Palmiotti
- Hilde D. de Vries
- Milaine V. Hovingh
- Martijn Koehorst
- Niels L. Mulder
- Esther Verkade
- Melany K. Veentjer
- Theo H. van Dijk
- Vincent W. Bloks
- Rick Havinga
- Henkjan J. Verkade
- Jan Freark de Boer
- Folkert Kuipers
Read more : Biomedicines :https://www.mdpi.com/2227-9059/11/9/2495
Last modified: | 11 September 2023 09.37 a.m. |
More news
-
04 July 2025
University of Groningen awards different prizes during Ceremony of Merits
The UG awarded different prizes to excellent researchers and students during the Ceremony of Merits on 4 July 2025.
-
02 July 2025
Relinde Weil reappointed as a member of the Supervisory Board UG
The Minister of Education has reappointed Relinde Weil for a second term as a member of the Supervisory Board of the University of Groningen.