The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells
The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells
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DOI：
10.1111/jnc.12646
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发表时间：
2014-05-01
影响因子：
4.7
通讯作者：
Heales, Simon J. R.
中科院分区：
文献类型：
--
作者：
Hughes, Sean David;Kanabus, Marta;Heales, Simon J. R.
生酮饮食（KD）是治疗耐药性癫痫的有效方法。然而，在依从性和耐受性方面存在困难。因此，需要能够复制生酮饮食功效的精炼/更简单的配方。提出的假设之一是生酮饮食会增加细胞线粒体含量，从而导致癫痫阈值升高。在这里，我们重点关注中链甘油三酯形式的饮食，并观察到服用中链甘油三酯 KD 的患者血浆辛酸 (C8) 和癸酸 (C10) 水平升高。使用神经元细胞系 (SH-SY5Y)，我们证明 250-M C10（而非 C8）在 6 天的时间内导致线粒体酶、柠檬酸合酶以及复合物 I 活性和过氧化氢酶活性显着增加。电子显微镜还表明线粒体数量增加。 C10 是一种已报道的过氧化物酶体增殖物激活剂受体激动剂，并且使用过氧化物酶体增殖剂激活剂受体拮抗剂已被证明可以阻止 C10 介导的线粒体含量和过氧化氢酶的增加。 C10 可能模仿与生酮饮食相关的线粒体增殖，并提出基于这种脂肪酸的配方可以取代更复杂的饮食的可能性。
The Ketogenic diet (KD) is an effective treatment with regards to treating pharmaco-resistant epilepsy. However, there are difficulties around compliance and tolerability. Consequently, there is a need for refined/simpler formulations that could replicate the efficacy of the KD. One of the proposed hypotheses is that the KD increases cellular mitochondrial content which results in elevation of the seizure threshold. Here, we have focussed on the medium-chain triglyceride form of the diet and the observation that plasma octanoic acid (C8) and decanoic acid (C10) levels are elevated in patients on the medium-chain triglyceride KD. Using a neuronal cell line (SH-SY5Y), we demonstrated that 250-M C10, but not C8, caused, over a 6-day period, a marked increase in the mitochondrial enzyme, citrate synthase along with complex I activity and catalase activity. Increased mitochondrial number was also indicated by electron microscopy. C10 is a reported peroxisome proliferator activator receptor agonist, and the use of a peroxisome proliferator activator receptor antagonist was shown to prevent the C10-mediated increase in mitochondrial content and catalase. C10 may mimic the mitochondrial proliferation associated with the KD and raises the possibility that formulations based on this fatty acid could replace a more complex diet.