In summary, the present study shows that the hepatic expression of SRA and ATGL is inversely correlated, and the loss of SRA in the mouse liver or hepatocytes upregulates the expression of ATGL primarily by promoting the inductive effect of FoxO1, which may lead to increased FFA β-oxidation and confer protection against hepatic steatosis in diet-induced obesity. The gene discussed is PNPLA2; the disease is obesity due to melanocortin 4 receptor deficiency.