Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

Nutrients. 2017 Oct 6;9(10):1100. doi: 10.3390/nu9101100.

Abstract

The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001). Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

Keywords: Fat-1 mice; hindlimb suspension; muscle disuse atrophy; protein synthesis/degradation signaling; ω-3 PUFAs.

MeSH terms

  • Adiposity
  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Glycogen Synthase Kinase 3 beta / biosynthesis
  • Hindlimb Suspension*
  • Isotonic Contraction
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Fatigue
  • Muscle Proteins / metabolism
  • Muscle Strength
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control*
  • Phenotype
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Signal Transduction
  • Time Factors
  • Tripartite Motif Proteins / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Cadherins
  • Muscle Proteins
  • Tripartite Motif Proteins
  • fat1 protein, mouse
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proteasome Endopeptidase Complex