To further clarify the role of Pin1 in NAFLD, we constructed an NAFLD model in Pin1 knockout mice and confirmed that knockdown of Pin1 reduced liver steatosis and fibrosis, while immunohistochemical results showed that knockdown of Pin1 could activate the AMPK/ACC1 signalling pathway and regulate the changes in its downstream target genes, reducing the lipid accumulation in the liver caused by NAFLD. Here, ACACA is linked to metabolic dysfunction-associated steatotic liver disease.