Oral PresentationBackground/Aims: The prevalence of obstructive sleep apnea (OSA) is high
in patients with non-alcoholic fatty liver disease (NAFLD) and NASH is a
progressive hallmark of the pathogenesis of NAFLD. Chronic intermittent
hypoxia is associated with recurrent episodes of oxygen desaturation and
reoxygenation in OSA patients, leading to excessive production of reactive
oxygen species (ROS). The causal link between OSA and NAFLD is not
known and the mechanistic effect of intermittent hypoxia (IH) on the
pathogenesis of NAFLD remains elusive. Here we tested the hypothesis that
IH-induced oxidative stress aggravates lipid accumulation and inflammation
induced by sodium palmitate in HepG2 cells.
Materials and Methods: HepG2 cells were treated with sodium palmitate
or vehicle under normoxia (Nx) or IH condition for 72 hours in the present
or absence of a ROS scavenger MnTBAP. Cell viability was detected by
MTT assay and intracellular lipid deposit was examined by oil red staining.
Lipid peroxidation was measured by malondialdehyde (MDA) assay and
levels of reactive oxygen species (ROS) were detected by CM-H2DCFDA
staining. The expressions of pro-inflammatory cytokines (IL-1β, TNF-α,
IL-6), fatty acid uptake-associated genes (caveolin-1 and FATP5), fatty acid
synthesis genes (SREBP1 and ACC1) and fatty acid β-oxidation gene ACOX
were determined by real-time PCR.
Results: Results showed that sodium palmitate increased lipid deposit in the
cells and it also decreased cell viability. The effect of sodium palmitate was
more prominent in the group co-treated with hypoxia. Levels of MDA and
ROS and the expressions of IL-1β, TNF-α, IL-6 and caveolin-1, but not
FATP5, were significantly increased in the palmitate- or hypoxia-treated
group and were remarkably elevated in the co-treated group. These effects
were abolished by MnTBAP treatment. In addition, levels of the expression
of ACOX, SREBP1 and ACC1 were significantly lowered in the cells treated
with palmitate or hypoxia and the expressions were much less in the cotreated
group. Treatment of MnTBAP prevented the decreased expression of
ACOX but had no effect on the SREBP1 and ACC1 expression.
Conclusion: IH-induced oxidative stress exacerbates lipid accumulation and
inflammation induced by sodium palmitate in HepG2 cells, probably mediated
by an increase in lipid uptake and a decrease in the fatty acid β-oxidation.published_or_final_versio
