Analysis Fxr-null mice18) and wild-type mice were housed under a standard 12-h light–dark cycle (9 am—9 pm). Before beginning the experiments, the mice were fed standard rodent chow (CE2; CLEA Japan, Tokyo, Japan) and water when needed. Age-matched groups of 8—10-week-old female mice were intravenously injected with recombinant FGF19 (400mg or 4mg/kg/d) or vehicle (saline) through the tail vein once a day for 3d. They were killed 6h after the final injection. Liver tissues were frozen in liquid nitrogen and stored at 80 C until use. For histological analysis, some of the frozen liver sections were stained with Oil Red O using standard procedures. All experiments were performed in accordance with the Guidelines for Animal Experiments of Tohoku University (Sendai, Japan). The protocol was approved by the Institutional Animal Care and Use Committee at Tohoku University (Permission No. 22-Pharm-Animal-6).