The Cyp2a5−/− mice (C57BL/6 background) were created by crossing male Cyp2a5−/− mice (Zhou et al., 2010) (kindly provided by Dr. Xinxin Ding, SUNY College of Nanoscale Science and Engineering, Albany, NY, USA) and female C57BL/6 wild-type mice (purchased from Charles River Laboratory, MA, USA). Littermates (Cyp2a5+/+) were bred as wild-type control. The Pparα−/− mice (B6.129S4 background; strain number 008154) were purchased from Jackson Laboratory. Pparα and Cyp2a5 double knockout mice (Pparα−/−/Cyp2a5−/−) were created by crossing the Pparα−/− mice with Cyp2a5−/− mice. Littermates (Pparα+/+/Cyp2a5−/−) were used as wild-type control mice. The 6th generation of mice were used for the experiments. Liver specific Fgf21 knockout (Fgf21alb-cre) mice and liver specific Fr1 knockout (Fr1alb-cre) mice were created by crossing Fgf21 floxed mice (purchased from Jackson Laboratory; B6.129S6 background; strain number 022361) and Fr1 floxed mice (B6.129S4 background; generously provided by Dr. Philippe Soriano, Department of Development and Regenerative Biology, Icahn School of Medicine at Mount Sinai, NY, USA) with transgenic Alb-Cre recombinase (purchased from Jackson Laboratory; (C57BL/6 x DBA)F2 background; strain number 003574), respectively. The littermates that do not express Alb-Cre recombinase were