In this study, by using the ApoE−/− mice, we hypothesized that 1) the combination of HFD, hyperlipidemia, and adiponectin knockdown may cause more severe insulin resistance and 2) that the insulin resistance ameliorating effects of liraglutide was, at least in part, due to increased FGF-21 activity. This evidence concerns the gene ADIPOQ and Insulin resistance.