Abstract
Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC-MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways.
Highlights
The initial use of ketogenic diets (KD) for epilepsy in humans was in the 1920s, in order to mimic the metabolic state and biochemical changes associated with fasting, as fasting was shown to possess anticonvulsant properties[1]
An ex vivo rat hippocampal slice model of epileptiform activity showed that capric acid, acting as a non-competitive antagonist, binds to Abbreviations: FA, fatty acids; KD, ketogenic diets; longchain TAG (LCT), long-chain TAG; LP, lipid profiling; MCFA, medium-chain fatty acids; MCT, medium-chain TAG; MCTD, medium-chain TAG diet; QC, quality control; Ultra-performance liquid chromatography coupled to MS (UPLC-MS), ultra-performance liquid chromatography-MS
Considering the rate at which MCT are normally metabolised compared with LCT, even if MCT and/or MCFA metabolites were initially detected in the fasted serum samples, their intensities may have been too low to either pass metabolite feature QC filtering protocols applied in this study or to be considered significant in subsequent statistical tests
Summary
The initial use of ketogenic diets (KD) for epilepsy in humans was in the 1920s, in order to mimic the metabolic state and biochemical changes associated with fasting, as fasting was shown to possess anticonvulsant properties[1]. A novel KD (medium-chain TAG diet (MCTD)) developed for canine consumption, with relatively low fat and medium-chain TAG (MCT) levels, was recently shown to significantly reduce both seizure frequency and the number of days with seizure occurrence in dogs with idiopathic epilepsy[7]. This MCTD contained caprylic (8 : 0), capric (10 : 0) and lauric (12 : 0) SFA[7], which is in accordance with the MCT content present in other MCT KD[8,9]. The primary aim of this study was to determine the global metabolic response of ketogenic MCTD consumption on serum biofluid metabolic profiles in dogs with idiopathic epilepsy
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