# MiR‐18a‐5p Attenuates Oxidative Stress and Inhibits Lipid Accumulation in Alcoholic Fatty Liver by Activating the CYP1A1‐PPAR Axis

## TL;DR

This study identifies a new pathway involving miR-18a-5p, CYP1A1, and PPAR that could help treat alcoholic fatty liver disease by reducing oxidative stress and lipid buildup.

## Contribution

The study reveals miR-18a-5p as a novel regulator of oxidative stress and lipid accumulation in alcoholic fatty liver disease via the CYP1A1-PPAR axis.

## Key findings

- MiR-18a-5p targets CYP1A1 to reduce oxidative stress in alcohol-induced liver cells.
- Inhibition of CYP1A1 by miR-18a-5p decreases lipid accumulation through modulation of PPARγ and PPARα.
- The miR-18a-5p/CYP1A1/PPAR axis is a potential therapeutic target for alcoholic fatty liver disease.

## Abstract

Lipid deposition in alcoholic fatty liver disease (AFL) represents an early stage in alcoholic liver disease progression and may contribute to carcinogenesis. MicroRNAs (miRNAs) play critical regulatory roles in liver biological processes.

In this study, we explored the miR‐18a‐5p/CYP1A1/PPAR axis in AFL using bioinformatics approaches. An AFL rat model was created, and second‐generation sequencing identified differentially expressed mRNA in rat liver tissues. Core genes were identified through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Gene Expression Omnibus database analyses. These genes were validated by qPCR in liver tissues and via in vitro experiments using L02 cells. The upstream miRNA identified in AFL was further verified in L02 cells using luciferase reporter assays.

Differential gene analysis revealed CYP1A1 and the PPAR pathway. In alcohol‐induced L02 cells, increased CYP1A1 expression promoted oxidative stress and altered lipid metabolism via the PPAR pathway. MiR‐18a‐5p was identified as an upstream regulator that targets CYP1A1 to ameliorate alcohol‐induced oxidative stress. Inhibition of CYP1A1 by miR‐18a‐5p improved the expression of PPARγ‐related genes and decreased PPARα‐related gene expression, thereby reducing lipid deposition.

The miR‐18a‐5p/CYP1A1/PPAR axis is a novel pathway that could be targeted for AFL treatment.