PDF(Pubmed)
Abstract：
The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.
摘要：
经典生酮饮食是耐药癫痫的有效治疗选择,但它的高脂肪含量挑战患者的依从性。通过比较底物的生酮潜力的方法来优化肝酮的产生，可能有助于降低饮食中的脂肪含量，而不会损失酮症的诱导。这里,我们提出了一种肝细胞测定法，测量脂肪酸底物的β-羟基丁酸酯（βHB）产量。即使包含4至18个碳原子的链状白蛋白缀合的脂肪酸也显示出S形浓度-βHB响应曲线（CRC），而乙酸盐和omega-3PUFA则不产生CRC。虽然CRC没有通过其半最大有效浓度(EC50)来区分，它们的最大反应不同，与碳链长度成反比，丁酸最高。该测定还适当地评估来自脂肪酸共混物的βHB产率,检测来自将中链脂肪酸交换为长链脂肪酸的最大响应的变化。该测定进一步检测到丁酸和己酸作为高浓度的生酮底物和低浓度的生酮增强剂的双重作用。增加油酸和脂肪酸混合物的βHB产率。该测定还发现丙酸盐在低生理浓度下抑制油酸和脂肪酸混合物的生酮作用。尽管体外测定法显示出有望作为优化脂肪混合物生酮产量的工具，其预测价值需要人工验证。
