Our results suggest that the effect of agmatine on the development of hepatic steatosis in Western HFD apoE−/− mice is related to inhibition of DNL, as evidenced by the significant decrease expression of key factors and enzymes involved in this lipogenic pathway, such as: SREBP-1c, fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1). Here, FASN is linked to fatty liver disease.