Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury

PLoS One. 2013 Jun 13;8(6):e64525. doi: 10.1371/journal.pone.0064525. Print 2013.

Abstract

The progressive deterioration of the neuromuscular axis is typically observed in degenerative conditions of the lower motor neurons, such as amyotrophic lateral sclerosis (ALS). Neurodegeneration in this disease is associated with systemic metabolic perturbations, including hypermetabolism and dyslipidemia. Our previous gene profiling studies on ALS muscle revealed down-regulation of delta-9 desaturase, or SCD1, which is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Interestingly, knocking out SCD1 gene is known to induce hypermetabolism and stimulate fatty acid beta-oxidation. Here we investigated whether SCD1 deficiency can affect muscle function and its restoration in response to injury. The genetic ablation of SCD1 was not detrimental per se to muscle function. On the contrary, muscles in SCD1 knockout mice shifted toward a more oxidative metabolism, and enhanced the expression of synaptic genes. Repressing SCD1 expression or reducing SCD-dependent enzymatic activity accelerated the recovery of muscle function after inducing sciatic nerve crush. Overall, these findings provide evidence for a new role of SCD1 in modulating the restorative potential of skeletal muscles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / rehabilitation
  • Animals
  • Disease Models, Animal
  • Down-Regulation
  • Gene Expression
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology*
  • Oxidation-Reduction
  • Phenotype
  • Recovery of Function
  • Stearoyl-CoA Desaturase / deficiency
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism*

Substances

  • Stearoyl-CoA Desaturase

Grants and funding

This work was supported by funds from European Community's Health Seventh Framework Programme under grant agreement no. 259867 (FP7/2007-2013) and Thierry Latran Foundation to JPL; “Appel à Projets 2009 du Conseil Scientifique” (University of Strasbourg) to JLGDA; and “Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone” to JLGDA and FR. GH is supported by the Higher Education Commission of the Pakistani government and “Association pour la Recherche et le Développement de Moyens de Lutte contre les Maladies Neurodégénératives” (AREMANE). FS is granted by “Association Française contre les Myopathies” and AREMANE. AH is a research fellow receiving funds from FP7/2007-2013. JLGDA is recipient of a “Chaire d'Exellence INSERM/Université de Strasbourg”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.