β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms
β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms
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DOI：
10.1007/s11064-016-2099-2
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Rae, Caroline D.
中科院分区：
文献类型：
--
作者：
Achanta, Lavanya B.;Rae, Caroline D.
β-羟基丁酸（β OHB）是一种酮体，被氧化为大脑燃料。虽然它对健康大脑中能量代谢的贡献是最小的，但它是一种有趣的代谢物，不仅被氧化，而且具有其他直接和附带的作用，使其成为用于治疗目的的感兴趣的分子。在脑中，β-OHB可以在星形胶质细胞中由脂肪酸的氧化或氨基酸的催化氧化产生，并且在所有脑细胞类型的线粒体中代谢，尽管穿过血脑屏障的摄取是代谢控制点。β OHB具有固有的高燃烧热，使其成为有效的线粒体燃料，其中它可以改变NAD（+）/NADH和Q/QH（2）对并减少线粒体活性氧的产生。它可以作为信号分子直接相互作用，影响K+通道的开放和Ca 2+通道的调节。β OHB是组蛋白脱乙酰酶的抑制剂，导致参与保护免受氧化应激和调节代谢的基因上调。它与免疫细胞中的炎性小体相互作用，以减少炎性细胞因子的产生并减轻炎症。使用β OHB作为有效的神经治疗剂依赖于增加血液β OHB水平，以鼓励β OHB进入大脑。虽然目前使用β OHB作为唯一治疗剂是有限的，但使用生酮饮食是一种更广泛使用的方法，最近对β OHB酯化形式的开发和测试显示出很大的希望，该方法提高了血浆β OHB，同时允许正常饮食的消耗。对β OHB作用机制的进一步了解将有助于更好地设计饮食和补充干预措施。
beta-Hydroxybutyrate (beta OHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain beta OHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point. beta OHB possesses an intrinsic high heat of combustion, making it an efficient mitochondrial fuel, where it can alter the NAD(+)/NADH and Q/QH(2) couples and reduce production of mitochondrial reactive oxygen species. It can directly interact as a signalling molecule influencing opening of K+ channels and regulation of Ca2+ channels. beta OHB is an inhibitor of histone deacetylases resulting in upregulation of genes involved in protection against oxidative stress and regulation of metabolism. It interacts with an inflammasome in immune cells to reduce production of inflammatory cytokines and reduce inflammation. Use of beta OHB as an efficient neurotherapeutic relies on increasing blood beta OHB levels so as to encourage entry of beta OHB to the brain. While use of beta OHB as a sole therapeutic is currently limited, with employment of a ketogenic diet a more widely used approach, recent development and testing of esterified forms of beta OHB have shown great promise, with the approach elevating plasma beta OHB while allowing consumption of normal diet. An improved understanding of the mechanisms by which beta OHB acts will allow better design of both diet and supplemental interventions.