We propose that elevated circulating levels of adiponectin are likely to promote the AMPK signaling pathway in hepatocytes, suppress de novo lipogenesis by inhibiting SREBP1c, ChREBP, ACC, and FAS, as well as suppressing ER stress by activating CPT-1 to improve the β-oxidation of FFAs, leading to significant increase in insulin sensitivity with protective effects against hepatic steatosis and insulin resistance. This evidence concerns the gene FAS and fatty liver disease.