Corroboratively, the present study showed that TM5441 activated PGC-1α, a mitochondrial biogenesis regulator, which might 1) increase fatty acid oxidation shown by increased lipolysis-related gene, decreased lipogenesis-related gene, and reduction of hepatic steatosis; 2) enhance insulin sensitivity, presented by insulin signaling activation, plasma insulin reduction, and normalization of GTT and ITT results. This evidence concerns the gene PPARGC1A and fatty liver disease.