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. 2015 Oct 1;14(6):1075–1084. doi: 10.1111/acel.12401

Figure 7.

Figure 7

Enhanced Exercise in AC5 KO mice through SIRT1 and MEK pathways. (A) Increased SIRT1 expression in gastrocnemius muscles of AC5 KO and AC5 SKM KO compared to WT mice, and FoxO3a expression was increased in skeletal muscle in AC5 KO compared to WT mice; n = 4–6. The effects of SIRT1 inhibition on exercise capacity in AC5 KO mice (B–E). (B) Enhanced exercise capacity in AC5 KO mice was abolished after treatment with SIRT1 inhibitor, EX 527. Only running distance is shown, but running time, maximum speed, and work to exhaustion were all attenuated similarly to running distance by the SIRT1 inhibitor. (C–E) Increased mitochondrial biogenesis, as reflected by mitochondrial DNA content, as well as increased citrate synthase and complex IV activities in AC5 KO mice, was abolished after treatment with the SIRT1 inhibitor, EX 527. *P < 0.01 vs. WT and **P < 0.05 vs. AC5 KO using one‐way ANOVA. There was no significant difference between AC5 KO treated with EX 527 and WT mice. Results are expressed as the mean ± SEM. (F) The effects of MEK inhibition on exercise capacity are shown in AC5 KO mice. Enhanced exercise capacity in AC5 KO mice was abolished after treatment with the MEK inhibitor, U0126. Exercise capacity in WT remained similar after treatment with MEK inhibitor. AC, adenylyl cyclase; KO, knock out.