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The dismantling of the neuromuscular junction is closely linked to chronic energy deficit found throughout the body. Metabolic (hypermetabolism and dyslipidemia) and mitochondrial alterations described in patients and murine models of ALS are associated with the development and progression of disease pathology and they appear long before motor neurons die. It is clear that these metabolic changes participate in the pathology of the disease. In this review, we summarize these changes seen throughout the course of the disease, and the subsequent impact of glucose\u2013fatty acid oxidation imbalance on disease progression. We also highlight studies that show that correcting this loss of metabolic flexibility should now be considered a major goal for the treatment of ALS.<\/jats:p>","DOI":"10.3390\/cells10061449","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:16:04Z","timestamp":1623248164000},"page":"1449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?"],"prefix":"10.3390","volume":"10","author":[{"given":"Cyril","family":"Quessada","sequence":"first","affiliation":[{"name":"M\u00e9canismes Centraux et P\u00e9riph\u00e9riques de la Neurod\u00e9g\u00e9n\u00e9rescence, INSERM, UMR_S 1118, Centre de Recherche de Biom\u00e9decine de Strasbourg (CRBS), Universit\u00e9 de Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bouscary","sequence":"additional","affiliation":[{"name":"M\u00e9canismes Centraux et P\u00e9riph\u00e9riques de la Neurod\u00e9g\u00e9n\u00e9rescence, INSERM, UMR_S 1118, Centre de Recherche de Biom\u00e9decine de Strasbourg (CRBS), Universit\u00e9 de Strasbourg, F-67000 Strasbourg, France"},{"name":"Neuro-Sys SAS, F-13120 Gardanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Ren\u00e9","sequence":"additional","affiliation":[{"name":"M\u00e9canismes Centraux et P\u00e9riph\u00e9riques de la Neurod\u00e9g\u00e9n\u00e9rescence, INSERM, UMR_S 1118, Centre de Recherche de Biom\u00e9decine de Strasbourg (CRBS), Universit\u00e9 de Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0914-6511","authenticated-orcid":false,"given":"Cristiana","family":"Valle","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Santa Lucia, Institute of Translational Pharmacology, CNR, 00133 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ferri","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Santa Lucia, Institute of Translational Pharmacology, CNR, 00133 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-2108","authenticated-orcid":false,"given":"Shyuan T.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"Centre for Clinical Research, The University of Queensland, Herston, QLD 4006, Australia"},{"name":"Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Loeffler","sequence":"additional","affiliation":[{"name":"M\u00e9canismes Centraux et P\u00e9riph\u00e9riques de la Neurod\u00e9g\u00e9n\u00e9rescence, INSERM, UMR_S 1118, Centre de Recherche de Biom\u00e9decine de Strasbourg (CRBS), Universit\u00e9 de Strasbourg, F-67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rowland, L.P., and Shneider, N.A. 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