{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T04:44:28Z","timestamp":1783831468174,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The medium\u2010chain triglyceride (MCT) ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Although the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain antiseizure effects, for example, peroxisome proliferator\u2010activated receptor\u2010\u03b3 (eliciting mitochondrial biogenesis and increased antioxidant status) and the \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate how this might occur, we measured the \u03b2\u2010oxidation rate of <jats:sup>13<\/jats:sup>C\u2010labeled C8 and C10 in neuronal <jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SY<\/jats:styled-content>5Y cells using isotope\u2010ratio mass spectrometry. The effects of carnitine palmitoyltransferase I (<jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>1) inhibition, with the <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>1 inhibitor etomoxir, on C8 and C10 \u03b2\u2010oxidation were also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both fatty acids were catabolized, as judged by <jats:sup>13<\/jats:sup><jats:styled-content style=\"fixed-case\">CO<\/jats:styled-content><jats:sub>2<\/jats:sub> release. However, C10 was \u03b2\u2010oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>1 activity, which is low in neurons, whereas 66% of C8 \u03b2\u2010oxidation was independent of <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>1. In addition, C10 \u03b2\u2010oxidation was decreased further in the presence of C8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>It is concluded that, because <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>1 is poorly expressed in the brain, C10 is relatively spared from \u03b2\u2010oxidation and can accumulate. This is further facilitated by the presence of C8 in the <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content> ketogenic diet, which has a sparing effect upon C10 \u03b2\u2010oxidation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13833","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T13:52:44Z","timestamp":1499349164000},"page":"1423-1429","source":"Crossref","is-referenced-by-count":56,"title":["Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium\u2010chain triglyceride ketogenic diet"],"prefix":"10.1111","volume":"58","author":[{"given":"Aziza","family":"Khabbush","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine UCL Great Ormond Street Institute of Child Health London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Orford","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine UCL Great Ormond Street Institute of Child Health London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery Department of Surgery Kaohsiung Medical University Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Vitaflo International Liverpool United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Vitaflo International Liverpool United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eaton","sequence":"additional","affiliation":[{"name":"Paediatric Surgery UCL Great Ormond Street Institute of Child Health London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J. 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