In addition, previous study showed that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) activated AMPK, which subsequently phosphorylates SREBP-2 in mouse livers, resulting in the amelioration of hepatic steatosis and hypercholesterolemia [29], while irisin improved hepatic steatosis via the sequential activation of AMPK and inhibition of SREBP-2 in high-fat diet-fed mice [30]. This evidence concerns the gene FNDC5 and fatty liver disease.