{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T18:49:57Z","timestamp":1784400597674,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,26]],"date-time":"2024-05-26T00:00:00Z","timestamp":1716681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171551"],"award-info":[{"award-number":["82171551"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20232ACB205002"],"award-info":[{"award-number":["20232ACB205002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["82171551"],"award-info":[{"award-number":["82171551"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Jiangxi Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["20232ACB205002"],"award-info":[{"award-number":["20232ACB205002"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency in Caenorhabditis elegans using spl-1 RNA interference. Within these SPL-deficient nematodes, we observed diminished motility and perturbed muscle fiber organization, correlated with the accumulation of sphingoid bases, their phosphorylated forms, and ceramides (collectively referred to as the \u201csphingolipid rheostat\u201d). The disturbance in mitochondrial morphology was also notable, as SPL functional loss resulted in heightened levels of reactive oxygen species. Remarkably, the administration of the antioxidant N-acetylcysteine (NAC) ameliorates locomotor impairment and rectifies muscle fiber disarray, underscoring its therapeutic promise for ceramide-accumulation-related muscle disorders. Our findings emphasize the pivotal role of SPL in preserving muscle integrity and advocate for exploring antioxidant interventions, such as NAC supplementation, as prospective therapeutic strategies for addressing muscle function decline associated with sphingolipid\/ceramide metabolism disruption.<\/jats:p>","DOI":"10.3390\/nu16111623","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T05:14:02Z","timestamp":1716786842000},"page":"1623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["N-Acetylcysteine Alleviates Impaired Muscular Function Resulting from Sphingosine Phosphate Lyase Functional Deficiency-Induced Sphingoid Base and Ceramide Accumulation in Caenorhabditis elegans"],"prefix":"10.3390","volume":"16","author":[{"given":"Min","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"You","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenying","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2716-2627","authenticated-orcid":false,"given":"Jingjing","family":"Duan","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Aging and Disease, Human Aging Research Institute (HARI), School of Life Science, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. 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