The current study indicated that oral melatonin (10 mg/kg), by influencing miR-34a/SIRT1/SREBP1 expression, ameliorated steatosis, ER stress, mitochondrial health and autophagy in high-fat diet-induced NAFLD in WT but not in HET mice. This evidence concerns the gene SREBF1 and metabolic dysfunction-associated steatotic liver disease.