FoxO-dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension

Muscle atrophy is a complex process that is in common with many different catabolic
diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy
programme in the different disuse/inactivity conditions have not yet been completely dissected.
The inhibition of FoxO is considered to only partially spare muscle mass after denervation. The
present study aimed: (i) to determine the involvement of FoxOs in hindlimb suspension disuse
model; (ii) to define whether the molecular events of protein breakdown are shared among
different unloaded muscles; and finally (iii) to compare the data obtained in this model with
another model of inactivity such as denervation. Both wild-type and muscle-specific FoxO1,3,4
knockout (FoxO1,3,4−/−) mice were unloaded for 3 and 14 days and muscles were characterized
by functional, morphological, biochemical and molecular assays. The data obtained show that
FoxOs are required for muscle loss and force drop during unloading. Moreover, we found
that FoxO-dependent atrogenes vary in different unloaded muscles and that they diverge from
denervation. The findings of the present study clearly indicate that the signalling network that
controls the atrophy programme is specific for each catabolic condition.