Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10504265" target="_blank" >RIV/00216208:11160/25:10504265 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1DYwEL63nf" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1DYwEL63nf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2025.118542" target="_blank" >10.1016/j.biopha.2025.118542</a>
Alternative languages
Result language
angličtina
Original language name
Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration
Original language description
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects a significant portion of the global population, with mitochondrial dysfunction playing a pivotal role in its pathogenesis. Although FXR agonists such as obeticholic acid (OCA) have been studied as potential treatments for MASLD, the direct effects of OCA on the liver are still not fully understood. This study aimed to evaluate the effects of OCA in an in vivo model of MASLD. Methods: Male C57BL/6 J mice were fed a control diet (CD) or a Western diet (WD) enriched with glucose and fructose in the drinking water for 36 weeks. During the final 3 weeks, mice received OCA (5 or 10 mg/kg/day) or vehicle. Liver histology, biochemical parameters, gene expression, mitochondrial enzymes activity and mitochondrial respiration were assessed. Results: WD-fed mice exhibited increased body and liver weights and elevated aminotransferases, none of which were altered by OCA. OCA treatment did not significantly impact steatosis, inflammation, fibrosis, or hepatic lipid content. WD feeding reduced succinate-stimulated hepatic mitochondrial respiration, associated with decreased succinate dehydrogenase (SDH) expression and activity. OCA partially restored Sdh subunits B and C expression but did not significantly improve respirometric parameters. Conclusion: Our findings consistently demonstrate that OCA administration in an established diet-induced murine model of MASLD does not improve hepatic steatosis or inflammation. Moreover, the WD-induced decrease in succinate-stimulated mitochondrial respiration was not ameliorated by OCA.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicine & Pharmacotherapy
ISSN
0753-3322
e-ISSN
1950-6007
Volume of the periodical
192
Issue of the periodical within the volume
NOV
Country of publishing house
FR - FRANCE
Number of pages
10
Pages from-to
118542
UT code for WoS article
999
EID of the result in the Scopus database
2-s2.0-105016255577