Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension

Abstract

Introduction: Hindlimb unloading-induced muscle atrophy is often assessed after a homeostatic state is established, thus overlooking the early adaptations that are critical to developing this pattern of atrophy.

Methods: Muscle function and physiology were characterized at 0, 1, 3, 7, and 14 days of hindlimb suspension (HS).

Results: Reductions in muscle mass were maximal by Day 14 of HS. Functional strength and isolated muscle strength were reduced. MyHC-I and -IIa expressing fibers were reduced in size by Day 7 in the soleus and by Day 14 in the gastrocnemius (MyHC-I fibers only). Atrogin-1 and MuRF1 expression was increased by Day 1 in both the calf and tibialis anterior while IGF-1 expression was significantly reduced on Day 3. Phosphorylation of Akt was reduced on Day 14.

Conclusions: Insight into these early changes in response to HS improves understanding of the molecular and functional changes that lead to muscle atrophy.

Keywords: hindlimb suspension; myosin heavy chain; protein degradation; skeletal muscle; strength.