Metformin and pioglitazone synergistically reduced ALT levels, liver weight, hepatic lipid droplets, FFA, DAG and TAG levels, along with decreased expression of genes associated with FFA uptake and de novo lipogenesis, such as Fads1, Fads2, Fasn, Scd1, Elovl5, Pklr and Cd36. Therefore, it is reasonable to suggest that the combination of metformin and pioglitazone might be a promising treatment strategy for NAFLD. The gene discussed is FADS1; the disease is metabolic dysfunction-associated steatotic liver disease.