FoxO1 does not limit growth in overloaded skeletal muscle

To determine the role of the FoxO1 protein in the regulation of skeletal muscle growth, plantaris muscles of 3‐month‐old male wildtype C57BL/6 (WT) and muscle‐specific transgenic mice overexpressing FoxO1 (FoxO1 +/−) were mechanically overloaded via synergist ablation (SA). Animals exposed to sham surgery (SH) served as controls. Following 14‐days of SA or SH, plantaris muscles were excised, weighed and SDS‐PAGE and western blot analyses performed to assess changes in total Akt, phospho‐Akt (Ser 473), total p70 s6k , and phospho‐p70 s6k (Thr 389). Plantaris muscles of control FoxO1+/− mice were significantly smaller compared to WT counterparts (17.3 ± 1.3 mg vs. 11.1 ± 1.4 mg), but responded similarly to 14‐days of mechanical overload (54% vs. 55% increase in muscle mass, respectively). Total and phosphorylated levels of p70 s6k were significantly suppressed in FoxO1+/− mice compared to WT counterparts following SA. Total and phosphorylated levels of Akt were increased in both WT and FoxO1+/− mice following SA. These preliminary findings indicate that although skeletal muscle of FoxO1 overexpressing mice are smaller in size, the FoxO1 protein does not limit the adaptive capability of these muscles to mechanical overload. The growth response exhibited in skeletal muscle of FoxO1+/− mice appears to be independent of p70 s6k regulation.