The central role of the Hh signaling pathway in liver steatosis is emphasized by our findings in vitro that activation of Hh signaling via the Sufu siRNA, recombinant SHH, the Hh agonist SAG and the combined overexpression of GLI1 and GLI3 was able to significantly reduce the expression of Srebf1 and mitigate the accumulation of lipids in steatotic hepatocytes. Here, GLI3 is linked to fatty liver disease.