USP7 overexpression in C57BL/6 mouse liver suppresses gluconeogenesis. A, Insulin signaling remains relatively unchanged in livers of mice overexpressing USP7. Western blot analysis of nuclear and cytosolic fractions from livers of 48-h fasted mice. B, Hepatic overexpression of wild-type USP7 suppresses gluconeogenic genes. Liver mRNA levels from mice in (A) are graphed relative to expression of GFP and presented as average ± SEM; n = 6–7. *, P < .05; **, P < .01; and ***, P < .001 by one-way ANOVA with Newman-Keuls Multiple Comparison test. C, USP7 overexpression improves pyruvate tolerance. Intraperitoneal (IP) pyruvate tolerance test from mice infected with GFP, wild-type USP7, or USP7 CS adenoviruses. Mice were fasted overnight prior to injection of 2 g/kg sodium pyruvate. Data are presented as change in glycemia following pyruvate injection and are from two independent experiments. Presented as average ± SEM. n = 9–19. *, P < .05 GFP vs USP7; and #, P < .05 USP7 vs USP7 CS by one-way ANOVA with Newman-Keuls Multiple Comparison test per time point.