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Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis

Abstract : Abstract 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 SOD1G93A 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.
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https://www.hal.inserm.fr/inserm-03376307
Contributor : Stéphane Dieterle Connect in order to contact the contributor
Submitted on : Wednesday, October 13, 2021 - 2:02:42 PM
Last modification on : Tuesday, October 19, 2021 - 3:33:22 AM
Long-term archiving on: : Friday, January 14, 2022 - 7:03:25 PM

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Frederik Steyn, Rui Li, Siobhan Kirk, Tesfaye Tefera, Teresa Xie, et al.. Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis. Brain Communications, Oxford University Press on behalf of the Guarantors of Brain, 2021, 2 (2), pp.fcaa154. ⟨10.1093/braincomms/fcaa154⟩. ⟨inserm-03376307⟩

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