{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:45:29Z","timestamp":1793850329439,"version":"4.6.1"},"reference-count":57,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["575466"],"award-info":[{"award-number":["575466"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010156379"],"award-info":[{"award-number":["PJT\u2010156379"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GUP15014"],"award-info":[{"award-number":["GUP15014"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["MU1415"],"award-info":[{"award-number":["MU1415"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["417757"],"award-info":[{"award-number":["417757"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000723","name":"Tenovus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK59637"],"award-info":[{"award-number":["DK59637"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2U2C\u2010DK093000"],"award-info":[{"award-number":["2U2C\u2010DK093000"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra\u2010neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed clinical data collected from a large cohort of pediatric SMA type I\u2013III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, <jats:italic>Smn<jats:sup>2B\/\u2010<\/jats:sup><\/jats:italic> mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non\u2010alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50855","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T13:06:18Z","timestamp":1564146378000},"page":"1519-1532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Abnormal fatty acid metabolism is a core component of spinal muscular atrophy"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-1195","authenticated-orcid":false,"given":"Marc\u2010Olivier","family":"Deguise","sequence":"first","affiliation":[{"name":"Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Centre for Neuromuscular Disease University of Ottawa Ottawa Ontario Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Baranello","sequence":"additional","affiliation":[{"name":"UO Neurologia dello Sviluppo Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy"},{"name":"The Dubowitz Neuromuscular Centre NIHR BRC University College London Great Ormond Street Institute of Child Health &amp; Great Ormond Street Hospital London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Mastella","sequence":"additional","affiliation":[{"name":"SAPRE\u2010UONPIA, Fondazione IRCCS C\u00e0' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Beauvais","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Faculty of Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Leone","sequence":"additional","affiliation":[{"name":"International Center for the Assessment of Nutritional Status (ICANS), Department of Food, Environmental and Nutritional Sciences (DeFENS) University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"De Amicis","sequence":"additional","affiliation":[{"name":"International Center for the Assessment of Nutritional Status (ICANS), Department of Food, Environmental and Nutritional Sciences (DeFENS) University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Battezzati","sequence":"additional","affiliation":[{"name":"International Center for the Assessment of Nutritional Status (ICANS), Department of Food, Environmental and Nutritional Sciences (DeFENS) University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Dunham","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology Children's and Women's Health Centre of B.C Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Selby","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics BC Children's Hospital Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Warman Chardon","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Centre for Neuromuscular Disease University of Ottawa Ottawa Ontario Canada K1H 8M5"},{"name":"Neuroscience Program, Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Pediatrics Children's Hospital of Eastern Ontario Ottawa Ontario Canada"},{"name":"Department of Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh J.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"College of Medicine &amp; Veterinary Medicine University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie L.","family":"Courtney","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"College of Medicine &amp; Veterinary Medicine University of Edinburgh Edinburgh United Kingdom"},{"name":"Centre for Discovery Brain Science University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alannah J.","family":"Mole","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"College of Medicine &amp; Veterinary Medicine University of Edinburgh Edinburgh United Kingdom"},{"name":"Centre for Discovery Brain Science University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Kubinski","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology Hannover Medical School Hannover Germany"},{"name":"Center of Systems Neuroscience Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Claus","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology Hannover Medical School Hannover Germany"},{"name":"Center of Systems Neuroscience Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay M.","family":"Murray","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"College of Medicine &amp; Veterinary Medicine University of Edinburgh Edinburgh United Kingdom"},{"name":"Centre for Discovery Brain Science University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Bowerman","sequence":"additional","affiliation":[{"name":"School of Medicine Keele University Staffordshire United Kingdom"},{"name":"Institute for Science and Technology in Medicine Stoke\u2010on\u2010Trent United Kingdom"},{"name":"Wolfson Centre for Inherited Neuromuscular Disease RJAH Orthopaedic Hospital Oswestry United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Gillingwater","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"College of Medicine &amp; Veterinary Medicine University of Edinburgh Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bertoli","sequence":"additional","affiliation":[{"name":"International Center for the Assessment of Nutritional Status (ICANS), Department of Food, Environmental and Nutritional Sciences (DeFENS) University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon H.","family":"Parson","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh United Kingdom"},{"name":"Institute of Medical Sciences University of Aberdeen Aberdeen United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-7310","authenticated-orcid":false,"given":"Rashmi","family":"Kothary","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa Ottawa Ontario Canada"},{"name":"Centre for Neuromuscular Disease University of Ottawa Ottawa Ontario Canada K1H 8M5"},{"name":"Department of Medicine University of Ottawa Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.134"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-803685-3.00007-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.08.019"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu142"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu189"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24549"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12546"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12793"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34635"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu052"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23582"},{"key":"e_1_2_8_14_1","first-page":"801","article-title":"Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice","volume":"26","author":"Deguise MO","year":"2017","journal-title":"Hum Mol Genet"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.423"},{"key":"e_1_2_8_16_1","first-page":"167","volume-title":"Spinal muscular atrophy: disease mechanisms and therapy","author":"Deguise MO"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq329"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt612"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22522"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.11.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2018.4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.09.023"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.04.024"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199903)45:3<337::AID-ANA9>3.0.CO;2-U"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(94)00100-G"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2012.01.004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200615"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213680"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.02.014"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807305788"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1542\/peds.89.3.495","article-title":"National Cholesterol Education Program (NCEP): highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents","volume":"89","author":"NCEP","year":"1992","journal-title":"Pediatrics"},{"key":"e_1_2_8_32_1","first-page":"4494","article-title":"Effect of genetic background on the phenotype of the Smn2B\/\u2010 mouse model of spinal muscular atrophy","volume":"25","author":"Eshraghi M","year":"2016","journal-title":"Hum Mol Genet"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)40190-7"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.11.1818"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2018.09.062"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1982"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.816769"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.02.010"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v2.i7.275"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-1212"},{"key":"e_1_2_8_42_1","first-page":"757","article-title":"Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention","volume":"5","author":"Millan J","year":"2009","journal-title":"Vasc Health Risk Manag"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28846"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.3216"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.110.957936"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0944"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-2980.2008.00331.x"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2016.1228286"},{"key":"e_1_2_8_49_1","first-page":"204","article-title":"Prevalence of metabolic syndrome and non\u2010alcoholic fatty liver disease in a cohort of italian patients with spinal\u2010bulbar muscular atrophy","volume":"37","author":"Francini\u2010Pesenti F","year":"2018","journal-title":"Acta Myol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022374"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700017-JLR200"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.51"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22106"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0638-1"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.0178"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X11430859"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63428-1"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpediatrics.2009.3"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facn3.50855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.50855","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.50855","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.50855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T01:59:46Z","timestamp":1694311186000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.50855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,26]]},"references-count":57,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/acn3.50855"],"URL":"https:\/\/doi.org\/10.1002\/acn3.50855","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,26]]},"assertion":[{"value":"2019-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}