hFGF21 cleavage activity in Fap knockout mice in vitro and in vivo.
A, immunoblot analysis to detect FAP in serum samples from Fap−/− mice and littermate controls (+/− and +/+) (n = 3 mice/group) (top). The same serum samples were mixed with recombinant hFGF21 (center) or hFGF21R (bottom) overnight and evaluated by immunoblot analysis to detect hFGF21. B, recombinant Fc-hFGF21 was injected intravenously into three +/+ (red lines), +/− (blue lines), or −/− (black lines) 6- to 8-week-old male mice at 20 mg/kg. Plasma was retrieved at the indicated time points and analyzed by intact FGF21 ELISA. Each point represents the intact hFGF21 concentration for one animal. **, p < 0.05; ***, p < 0.005 versus the wild-type control by two-tailed Student's t test (n = 3 mice/group).