Based on preclinical data in hepatocytes, FGF21 is thought to affect hepatic steatosis by modulating AMPK phosphorylation to regulate lipid accumulation, reducing sterol regulatory element-binding transcription factor 1 (SREBF1) to inhibit lipid synthesis, increasing PPARα mRNA and PPARα translocation into the nucleus to impact fatty acid oxidation and promoting lipid transport and secretion of VLDL21. This evidence concerns the gene PPARA and fatty liver disease.