Inhibiting hepatocyte ALKBH5 for MAFLD

Inhibiting hepatocyte activity of the demethylase ALKBH5, which removes N6-methyladenosine (m6A) modifications from RNA, could help treat metabolic dysfunction-associated fatty liver disease (MAFLD) by reducing mRNA expression of the glucagon receptor and epidermal growth factor receptor, thus decreasing gluconeogenesis and lipogenesis, respectively.

Proteomic analysis identified higher ALKBH5 expression in livers from mice with genetically induced MAFLD than in those from healthy controls. ALKBH5 protein expression was higher in livers from mice with genetically induced MAFLD or high fat diet-induced obesity than in those from healthy controls. Phosphorylated ALKBH5 levels were higher in livers from mice with genetically induced MAFLD than in those from healthy controls. ...