In the present study, we observed SR4 activates AMPK in the liver of HFD obese mice and reduced the mRNA expression of key lipogenic genes including Acaca, Fasn, Scd1, Cpt1a, Pparγ, Hmgcr, as well as the transcription factor Srebf1, leading to the suppression of de novo lipid production and eventually inhibition of hepatic steatosis. The gene discussed is SREBF1; the disease is fatty liver disease.