Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil.

Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil.
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患有生酮中链甘油三酸酯(MCT)油的特发性癫痫的狗的代谢指纹。

DOI:
10.3389/fvets.2022.935430
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发表时间:
2022
影响因子:
3.2
通讯作者:
--
中科院分区:
农林科学2区
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--
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中链甘油三酯(MCT)的摄入已被证明可改善癫痫犬的癫痫发作控制,减少行为合并症并改善认知功能。然而,受饮食MCT影响的确切代谢途径仍然知之甚少。在本研究中,我们旨在确定与特发性癫痫(IE)犬中摄入MCT补充剂(MCT-DS)相关的癫痫和行为合并症相关的代谢组和神经递质水平变化。在一项为期6个月的多中心、前瞻性、随机化、双盲、对照交叉试验设计中,评价了市售MCT-DS在28只IE犬群体中诱导的代谢变化。向犬的稳定基础饲料中补充基于代谢能量需求量的9% MCT或对照油,持续3个月,然后再补充替代油3个月。将经验证的定量核磁共振(NMR)光谱平台应用于餐前和餐后采集的血清样本,以比较DS和基线之间的代谢特征。此外,尿神经递质水平的变化进行了探讨。5只犬(30%)的癫痫发作频率总体降低≥ 50%,被归类为MCT应答者,而23只犬显示降低≤50%,被定义为MCT非应答者。与对照油相比,MCT消耗量对氨基酸代谢产生显着影响。虽然血清中总脂肪酸的浓度在两种补充剂中似乎相似,但个体脂肪酸的相对浓度不同。在MCT补充期间,多不饱和脂肪酸和花生四烯酸的浓度显著高于对照油。补充MCT时β-羟基丁酸水平显著更高。总体而言,9种神经递质中有4种发生显著改变:在MCT阶段检测到γ-氨基丁酸(GABA)浓度显著增加,伴随GABA-谷氨酸平衡的显著变化。MCT应答者在摄入MCT后尿中组胺、谷氨酸和5-羟色胺浓度显著降低。总之,这些新数据强调了MCT补充引起的脂质、氨基酸和酮代谢的代谢变化。了解MCT的代谢反应为开发更好的营养管理提供了新的途径,改善了癫痫和其他行为障碍犬的抗癫痫发作和神经保护作用。
Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. β-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.
DOI: 10.1111/jvim.16298
发表时间: 2022-01
影响因子: 2.6
作者:
Walker HK;Ottka C;Lohi H;Handel I;Clements DN;Gow AG;Mellanby RJ
通讯作者: Mellanby RJ