Nonalcoholic fatty liver disease (
NAFLD) is characterized by high morbidity. Although long noncoding RNAs (lncRNAs) are known to have a role in
NAFLD pathogenesis, the identified
lncRNA types are limited. In this study,
NAFLD models were established in vitro and in vivo using
free fatty acid-treated LO2 cells and high-fat diet-fed mice, respectively. Microarray data were downloaded from the Gene Expression Omnibus database, and AC012668 was selected for further analysis. Cell viability and apoptosis were measured using Cell Counting Kit 8 and flow cytometry assays.
RNA expression was detected using reverse transcription-quantitative polymerase chain reaction.
Triglyceride (TG) content and
lipid deposition were detected using
enzyme-linked
immunosorbent assay and
Oil-Red O staining. Western blotting was used to visualize
protein expression. Starbase and TargetScan were used to predict the target
miRNA and gene, and the predictions were verified through
RNA pull-down and
luciferase reporter assays. AC012668 expression levels were significantly suppressed in
NAFLD models, whereas AC012668 overexpression inhibited lipogenesis-related gene (SCD1, SREBP1, FAS) expression and TG/
lipid accumulation in vitro. Subsequently, miR-380-5p was predicted and verified to target AC012668, and its expression was notably increased in the
NAFLD cell model. Moreover, transfection of miR-380-5p antagonized the effects of AC012668 on
lipid formation and accumulation. LRP2 was confirmed to be the target gene of miR-380-5p and was downregulated in the
NAFLD cell model. Silencing LRP2 reversed the effects of the miR-380-5p inhibitor on
lipid formation and accumulation. AC012668 inhibited
NAFLD progression via the miR-380-5p/LRP2 axis. These findings may provide a novel strategy against
NAFLD.