PPARA and fatty liver disease: Hepatic deletion of Sirt1 facilitates the development of hepatic steatosis in response to ethanol feeding in mice, mainly by altering the function of LIPIN1, a transcriptional regulator of lipid metabolism.38 In addition, SIRT1 is a key regulator of Pparα signaling, which is the major regulator stimulating hepatic mitochondrial β-oxidation of fatty acids.