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

The result's identifiers

  • Result code in 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>

  • Alternative codes found

    RIV/00216208:11160/24:10478451

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30105 - Physiology (including cytology)

Result continuities

  • Project

    <a href="/en/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Pre-application research into innovative medicines and medical technologies</a><br>

  • Continuities

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

Others

  • Publication year

    2024

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    International Journal of Molecular Medicine

  • ISSN

    1107-3756

  • e-ISSN

    1791-244X

  • Volume of the periodical

    53

  • Issue of the periodical within the volume

    2

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    15

  • Pages from-to

    18

  • UT code for WoS article

    001140754700001

  • EID of the result in the Scopus database

    2-s2.0-85182027146