Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F20%3A10411153" target="_blank" >RIV/00216208:11150/20:10411153 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eihrny1hVN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=eihrny1hVN</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21031101" target="_blank" >10.3390/ijms21031101</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease

Popis výsledku v původním jazyce

Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.

Název v anglickém jazyce

Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease

Popis výsledku anglicky

Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LTC17044" target="_blank" >LTC17044: Jaterní mitochondrie – zaměření na vliv věku, životního stylu a prostředí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences [online]

ISSN

1422-0067

e-ISSN

—

Svazek periodika

21

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

1101

Kód UT WoS článku

000522551607028

EID výsledku v databázi Scopus

2-s2.0-85079129783