Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biomedicine &amp; Pharmacotherapy

ISSN

0753-3322

e-ISSN

1950-6007

Svazek periodika

192

Číslo periodika v rámci svazku

NOV

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

10

Strana od-do

118542

Kód UT WoS článku

999

EID výsledku v databázi Scopus

2-s2.0-105016255577