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

Muscle Nerve. 2013 Sep;48(3):393-402. doi: 10.1002/mus.23753. Epub 2013 Jul 24.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Adaptation, Biological / physiology*
  • Analysis of Variance
  • Animals
  • Body Mass Index
  • Electric Stimulation
  • Exercise Test
  • Gene Expression Regulation / physiology*
  • Hindlimb Suspension*
  • Insulin-Like Growth Factor I / metabolism
  • Longitudinal Studies
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fatigue / physiology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Proteins / metabolism
  • Muscle Strength
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / physiology*
  • Myosin Heavy Chains / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Time Factors
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Muscle Proteins
  • Tripartite Motif Proteins
  • Insulin-Like Growth Factor I
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • Myosin Heavy Chains