title: Systemic down-regulation of delta-9 desaturase promotes muscle oxidative metabolism and accelerates muscle function recovery following nerve injury.
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.
authors.affiliation: INSERM, U1118, Mécanismes Centraux et Péripheriques de la Neurodégénérescence, Strasbourg, France.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Hussain
authors.forename: Florent
authors.initials: F
authors.lastname: Schmitt
authors.forename: Alexandre
authors.initials: A
authors.lastname: Henriques
authors.forename: Thiebault
authors.initials: T
authors.lastname: Lequeu
authors.forename: Frederique
authors.initials: F
authors.lastname: Rene
authors.forename: Françoise
authors.initials: F
authors.lastname: Bindler
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dirrig-Grosch
authors.forename: Hugues
authors.initials: H
authors.lastname: Oudart
authors.forename: Lavinia
authors.initials: L
authors.lastname: Palamiuc
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Eric
authors.initials: E
authors.lastname: Marchioni
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Gonzalez De Aguilar
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000534:rehabilitation; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D010084:Oxidation-Reduction; D010641:Phenotype; D020127:Recovery of Function; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D013230:Stearoyl-CoA Desaturase