Effect of Mettl3 overexpression on gene expression in the livers of mice subjected to chronic-plus-binge ethanol feeding

Alcohol-associated steatohepatitis (ASH), a severe form of alcohol-associated liver disease (ALD), is characterized by pronounced steatosis and immune cells infiltration. As an inflammatory disease, ASH still lacks effective immunotherapies, and the mechanisms underlying alcohol-induced immune imbalance in the liver microenvironment remain elusive. RNA modifications are known to maintain hepatic homeostasis during physiological and pathological processes. This study aimed to investigate the alteration of RNA modification in ASH and its specific roles in regulating immune homeostasis. Our study found that the level of RNA N6-methyladenosine (m6A) modification and its key writer, METTL3, are markedly reduced in mouse liver during ASH. Hepatocyte-specific Mettl3 overexpression alleviated ASH by improving liver steatosis and inhibiting neutrophils infiltration and inflammatory cytokines production.