Our studies showed that EC-SOD might be a potential therapeutic agent for NAFLD through the direct activation of AMPK-PGC-1α and AMPK-FoxO1 signaling in hepatocytes, which modulates lipid metabolism, leading to anti-inflammatory, antioxidative and antiapoptotic effects and improving autophagy in the liver. The gene discussed is PRKAA1; the disease is metabolic dysfunction-associated steatotic liver disease.