Regarding the mechanisms by which the dietary DHA could ameliorate the aggravation of NAFLD induced by the diet high in saturated fat during aging, our data revealed that mice receiving dietary DHA showed a significant reduced expression of lipogenic genes such as Dgat2, Scd1, and Srebp1c. These data suggest that long-term dietary feeding (12 months) with DHA, even in the context of a HFD, modifies lipid liver metabolism balance, reducing the pathways favoring TG accumulation, and preventing the progression of NAFLD in obese mice during aging. Here, SREBF1 is linked to metabolic dysfunction-associated steatotic liver disease.