In summary, our studies elucidated that the SIRT1 activator E1231 decreased the expression of key lipogenesis-related proteins SREBP-1c, ACC and SCD-1 by activating the SIRT1-AMPKα pathway, and thereby inhibited hepatocyte lipid accumulation and improved hepatocyte steatosis, which ultimately had an improvement effect on NAFLD. Here, SCD is linked to metabolic dysfunction-associated steatotic liver disease.