Department of Integrative Biology and Physiology.
Division of Molecular Medicine, Department of Medicine.
Curr Opin Clin Nutr Metab Care. 2018 Jul;21(4):260-266. doi: 10.1097/MCO.0000000000000475.
Ketone body metabolism is a dynamic and integrated metabolic node in human physiology, whose roles include but extend beyond alternative fuel provision during carbohydrate restriction. Here we discuss the most recent observations suggesting that ketosis coordinates cellular function via epigenomic regulation.
Ketosis has been linked to covalent modifications, including lysine acetylation, methylation, and hydroxybutyrylation, to key histones that serve as dynamic regulators of chromatin architecture and gene transcription. Although it remains to be fully established whether these changes to the epigenome are attributable to ketone bodies themselves or other aspects of ketotic states, the regulated genes mediate classical responses to carbohydrate restriction.
Direct regulation of gene expression may occur in-vivo via through ketone body-mediated histone modifications during adherence to low-carbohydrate diets, fasting ketosis, exogenous ketone body therapy, and diabetic ketoacidosis. Additional convergent functional genomics, metabolomics, and proteomics studies are required in both animal models and in humans to identify the molecular mechanisms through which ketosis regulates nuclear signaling events in a myriad of conditions relevant to disease, and the contexts in which the benefits of ketosis might outweigh the risks.
酮体代谢是人体生理学中一个动态而综合的代谢节点，其作用不仅限于在碳水化合物限制期间提供替代燃料。在这里，我们讨论了最近的观察结果，表明酮症通过表观遗传调控来协调细胞功能。
酮症与包括赖氨酸乙酰化、甲基化和羟丁酰化在内的共价修饰有关，这些修饰作用于关键组蛋白，作为染色质结构和基因转录的动态调节剂。尽管这些表观基因组的改变是否归因于酮体本身或酮症状态的其他方面仍有待充分确定，但受调控的基因介导了对碳水化合物限制的经典反应。
在遵循低碳水化合物饮食、禁食酮症、外源性酮体治疗和糖尿病酮症酸中毒期间，通过酮体介导的组蛋白修饰，可能会在体内直接调节基因表达。需要在动物模型和人类中进行更多的功能基因组学、代谢组学和蛋白质组学研究，以确定酮症调节与疾病相关的多种情况下核信号事件的分子机制，以及酮症的益处超过风险的情况。
