Our results showed that VEGFB gene suppression can reduce the level of AMPK phosphorylation through CaMKKβ, inhibit ACC/CPT1 pathway and affect fatty acid oxidation, meanwhile, it could promote the SREBP1/Scd1 pathway and lead to lipogenesis and accelerate the development of NAFLD. Here, SREBF1 is linked to metabolic dysfunction-associated steatotic liver disease.