FGF21 exerts its effect via binding to and activating FR1 (Potthoff et al., 2012). Adipose tissues have comparatively high expression of FR1 (Fisher et al., 2011); FR1 expression in liver is only about 10% the level of expression detected in adipose tissue (Fisher et al., 2011), which leads to an expectation that FGF21 acts on adipose tissue to a greater extent than liver. We found that alcoholic fatty liver was comparable in the Fr1alb-cre mice and Fr1fl/fl mice, suggesting that FGF21 does not exert its lipid modulating effects through liver FR1. About 60% of hepatic fat is derived from adipose tissues (Donnelly et al., 2005), and adipose tissues play a very important role in the development of alcoholic fatty liver disease (Poggi and Di Luzio, 1964; Horning et al., 1960; Zhong et al., 2012). We plan to create adipose specific Fr1 knockout mice to address whether FGF21 exerts its effects through adipose FR1.
