Laboratory of Metabolic Medicine, Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.
Nutrients. 2024 Oct 18;16(20):3526. doi: 10.3390/nu16203526.
BACKGROUND/OBJECTIVES: Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy.
Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states.
Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed.
Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.
背景/目的：通过治疗性营养酮症提高酮体水平有助于代谢管理与癫痫、糖尿病、肥胖、癌症和神经退行性疾病相关的疾病过程。通过各种饮食策略可以实现营养酮症，例如经典的生酮饮食、改良的阿特金斯饮食、热量限制、周期性禁食或外源性生酮补充剂的摄入，如中链甘油三酯 (MCT)。然而，这些各种策略可能令人不快且难以遵循，因此实现和维持营养酮症可能是一个主要挑战。因此，研究人员继续探索外源性酮补充剂的科学和应用，作为进一步增强这种代谢治疗疗效的手段。
在这里，我们描述了一种结构新颖的合成甘油三酯，甘油三乙酰乙酸酯 (Gly-3AcAc)，我们从甘油和乙酰乙酸前体制备而成，当在禁食和不禁食条件下给予小鼠时，该前体在治疗范围内（2-3 mM）产生高酮血症。进行了动物研究以评估系统性引发酮症反应系统的潜在影响。在禁食和不禁食的饮食状态下，在雄性 VM/Dk 小鼠中测定了急性效应（24 小时或更短时间）。
在两种情况下，血液中的β-羟丁酸浓度升高（βHB；2-3 mM）。仅在禁食状态下葡萄糖水平降低。没有观察到有害的副作用。
在进一步研究之前，这种新型化合物可能会增加诱导治疗性营养酮症的方法。
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