The PI3K/Akt/mTOR pathway is up‐regulated during skeletal muscle hypertrophy in humans

We sought to resolve which components of the IGF1/PI3K/Akt/mTOR pathway are responsive to mechanical load and are coincident with increases in myofiber hypertrophy in vivo . A mixed‐age, mixed‐gender population (n = 66) of humans underwent a 16 wk lower extremity resistance training regimen. Muscle biopsies were performed at baseline and 24 h after the first and last loading bouts. Subjects were statistically clustered based on changes in mean fiber area (MFA, μm 2 ) as non‐responders (NR, n=17), modest responders (MR, +1111 μm 2 , n=32), and extreme responders (XR, +2475 μm 2 , n=17). Translation initiation signaling was assessed in a subset of 8 NR, 14 MR, and 8 XR. Data were analyzed via 3 x 3 (response cluster x time) repeated measures ANOVA. Tukey HSD tests were performed post hoc to localize main and/or interaction effects. Main time effects (P<0.05) were noted for p‐Akt (+53% after 1 bout), total Akt (+31% by wk 16), total 4EBP1 (−28% by wk 16), p‐eIF4E (+24% after 1 bout), total eIF4E (+15% after 1 bout), and p‐eIF4G (+51% after 1 bout). p‐4EBP1 tended to increase (24%, P=0.051) after 1 bout. Akt phosphorylation was 74% higher (P<0.05) and mTOR expression tended to be higher (44%, P=0.062) in XR vs. NR. Although further study is needed, the findings suggest differential responses of this pathway may partially explain marked differences in rates of hypertrophy between XR and NR. Support: R01 AG017896 and VA Merit.