Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis.
Fiche publication
Date publication
janvier 2020
Journal
Brain communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LOEFFLER Jean-Philippe
Tous les auteurs :
Steyn FJ, Li R, Kirk SE, Tefera TW, Xie TY, Tracey TJ, Kelk D, Wimberger E, Garton FC, Roberts L, Chapman SE, Coombes JS, Leevy WM, Ferri A, Valle C, René F, Loeffler JP, McCombe PA, Henderson RD, Ngo ST
Lien Pubmed
Résumé
Amyotrophic lateral sclerosis is characterized by the degeneration of upper and lower motor neurons, yet an increasing number of studies in both mouse models and patients with amyotrophic lateral sclerosis suggest that altered metabolic homeostasis is also a feature of disease. Pre-clinical and clinical studies have shown that modulation of energy balance can be beneficial in amyotrophic lateral sclerosis. However, the capacity to target specific metabolic pathways or mechanisms requires detailed understanding of metabolic dysregulation in amyotrophic lateral sclerosis. Here, using the superoxide dismutase 1, glycine to alanine substitution at amino acid 93 (SOD1) mouse model of amyotrophic lateral sclerosis, we demonstrate that an increase in whole-body metabolism occurs at a time when glycolytic muscle exhibits an increased dependence on fatty acid oxidation. Using myotubes derived from muscle of amyotrophic lateral sclerosis patients, we also show that increased dependence on fatty acid oxidation is associated with increased whole-body energy expenditure. In the present study, increased fatty acid oxidation was associated with slower disease progression. However, within the patient cohort, there was considerable heterogeneity in whole-body metabolism and fuel oxidation profiles. Thus, future studies that decipher specific metabolic changes at an individual patient level are essential for the development of treatments that aim to target metabolic pathways in amyotrophic lateral sclerosis.
Mots clés
amyotrophic lateral sclerosis, fatty acid oxidation, glucose oxidation, hypermetabolism, skeletal muscle
Référence
Brain Commun. 2020 ;2(2):fcaa154