l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats

Appl Physiol Nutr Metab. 2016 Dec;41(12):1240-1247. doi: 10.1139/apnm-2016-0094. Epub 2016 Aug 17.

Abstract

l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg-1·day-1) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

Keywords: apesanteur; atrophie musculaire; catabolic condition; condition catabolique; hindlimb suspension; l-carnitine; muscle atrophy; muscle-specific ubiquitin E3 ligases; suspension par les membres postérieurs; ubiquitine-ligase E3 spécifique au muscle; weightless.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Carnitine / therapeutic use*
  • Dietary Supplements*
  • Enzyme Repression*
  • Hindlimb Suspension / adverse effects
  • Immunohistochemistry
  • Male
  • Muscle Proteins / antagonists & inhibitors*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control
  • Muscular Disorders, Atrophic / etiology
  • Muscular Disorders, Atrophic / metabolism
  • Muscular Disorders, Atrophic / pathology
  • Muscular Disorders, Atrophic / prevention & control*
  • Proteasome Endopeptidase Complex
  • Proteasome Inhibitors / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Wistar
  • SKP Cullin F-Box Protein Ligases / antagonists & inhibitors*
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination
  • Weightlessness / adverse effects

Substances

  • Biomarkers
  • Muscle Proteins
  • Proteasome Inhibitors
  • Tripartite Motif Proteins
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Proteasome Endopeptidase Complex
  • Carnitine