Comparison of HepaRG and HepG2 cell lines to model mitochondrial respiratory adaptations in non-alcoholic fatty liver disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F24%3A10478451" target="_blank" >RIV/00216208:11150/24:10478451 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/24:10478451

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/ijmm.2023.5342" target="_blank" >10.3892/ijmm.2023.5342</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Comparison of HepaRG and HepG2 cell lines to model mitochondrial respiratory adaptations in non-alcoholic fatty liver disease

Popis výsledku v původním jazyce

Although some clinical studies have reported increased mitochondrial respiration in patients with fatty liver and early non-alcoholic steatohepatitis (NASH), there is a lack of in vitro models of non-alcoholic fatty liver disease (NAFLD) with similar findings. Despite being the most commonly used immortalized cell line for in vitro models of NAFLD, HepG2 cells exposed to free fatty acids (FFAs) exhibit a decreased mitochondrial respiration. On the other hand, the use of HepaRG cells to study mitochondrial respiratory changes following exposure to FFAs has not yet been fully explored. Therefore, the present study aimed to assess cellular energy metabolism, particularly mitochondrial respiration, and lipotoxicity in FFA-treated HepaRG and HepG2 cells. HepaRG and HepG2 cells were exposed to FFAs, followed by comparative analyses that examained cellular metabolism, mitochondrial respiratory enzyme activities, mitochondrial morphology, lipotoxicity, the mRNA expression of selected genes and triacylglycerol (TAG) accumulation. FFAs stimulated mitochondrial respiration and glycolysis in HepaRG cells, but not in HepG2 cells. Stimulated complex I, II-driven respiration and beta-oxidation were linked to increased complex I and II activities in FFA-treated HepaRG cells, but not in FFA-treated HepG2 cells. Exposure to FFAs disrupted mitochondrial morphology in both HepaRG and HepG2 cells. Lipotoxicity was induced to a greater extent in FFA-treated HepaRG cells than in FFA-treated HepG2 cells. TAG accumulation was less prominent in HepaRG cells than in HepG2 cells. On the whole, the present study demonstrates that stimulated mitochondrial respiration is associated with lipotoxicity in FFA-treated HepaRG cells, but not in FFA-treated HepG2 cells. These findings suggest that HepaRG cells are more suitable for assessing mitochondrial respiratory adaptations in the developed in vitro model of early-stage NASH.

Název v anglickém jazyce

Comparison of HepaRG and HepG2 cell lines to model mitochondrial respiratory adaptations in non-alcoholic fatty liver disease

Popis výsledku anglicky

Although some clinical studies have reported increased mitochondrial respiration in patients with fatty liver and early non-alcoholic steatohepatitis (NASH), there is a lack of in vitro models of non-alcoholic fatty liver disease (NAFLD) with similar findings. Despite being the most commonly used immortalized cell line for in vitro models of NAFLD, HepG2 cells exposed to free fatty acids (FFAs) exhibit a decreased mitochondrial respiration. On the other hand, the use of HepaRG cells to study mitochondrial respiratory changes following exposure to FFAs has not yet been fully explored. Therefore, the present study aimed to assess cellular energy metabolism, particularly mitochondrial respiration, and lipotoxicity in FFA-treated HepaRG and HepG2 cells. HepaRG and HepG2 cells were exposed to FFAs, followed by comparative analyses that examained cellular metabolism, mitochondrial respiratory enzyme activities, mitochondrial morphology, lipotoxicity, the mRNA expression of selected genes and triacylglycerol (TAG) accumulation. FFAs stimulated mitochondrial respiration and glycolysis in HepaRG cells, but not in HepG2 cells. Stimulated complex I, II-driven respiration and beta-oxidation were linked to increased complex I and II activities in FFA-treated HepaRG cells, but not in FFA-treated HepG2 cells. Exposure to FFAs disrupted mitochondrial morphology in both HepaRG and HepG2 cells. Lipotoxicity was induced to a greater extent in FFA-treated HepaRG cells than in FFA-treated HepG2 cells. TAG accumulation was less prominent in HepaRG cells than in HepG2 cells. On the whole, the present study demonstrates that stimulated mitochondrial respiration is associated with lipotoxicity in FFA-treated HepaRG cells, but not in FFA-treated HepG2 cells. These findings suggest that HepaRG cells are more suitable for assessing mitochondrial respiratory adaptations in the developed in vitro model of early-stage NASH.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Předaplikační výzkum inovativních léčiv a medicínských technologií</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Medicine

ISSN

1107-3756

e-ISSN

1791-244X

Svazek periodika

53

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

18

Kód UT WoS článku

001140754700001

EID výsledku v databázi Scopus

2-s2.0-85182027146