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Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet
Author(s) -
Khabbush Aziza,
Orford Michael,
Tsai YiChen,
Rutherford Tricia,
O'Donnell Maura,
Eaton Simon,
Heales Simon J. R.
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13833
Subject(s) - decanoic acid , ketogenic diet , triglyceride , carnitine palmitoyltransferase i , chemistry , carnitine , medicine , beta oxidation , endocrinology , peroxisome , medium chain triglyceride , mitochondrial biogenesis , biochemistry , fatty acid , receptor , cholesterol , biology , mitochondrion , epilepsy , neuroscience
Summary Objective The medium‐chain 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‐activated receptor‐γ (eliciting mitochondrial biogenesis and increased antioxidant status) and the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain. Methods To investigate how this might occur, we measured the β‐oxidation rate of 13 C‐labeled C8 and C10 in neuronal SH ‐ SY 5Y cells using isotope‐ratio mass spectrometry. The effects of carnitine palmitoyltransferase I ( CPT 1) inhibition, with the CPT 1 inhibitor etomoxir, on C8 and C10 β‐oxidation were also investigated. Results Both fatty acids were catabolized, as judged by 13 CO 2 release. However, C10 was β‐oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on CPT 1 activity, which is low in neurons, whereas 66% of C8 β‐oxidation was independent of CPT 1. In addition, C10 β‐oxidation was decreased further in the presence of C8. Significance It is concluded that, because CPT 1 is poorly expressed in the brain, C10 is relatively spared from β‐oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β‐oxidation.