PDF(Pubmed)
Abstract：
Overactivation of the NLRP3 inflammasome is implicated in chronic low-grade inflammation associated with various disease states, including obesity, type 2 diabetes, atherosclerosis, Alzheimer\'s disease, and Parkinson\'s disease. Emerging evidence, mostly from cell and animal models of disease, supports a role for ketosis in general, and the main circulating ketone body beta-hydroxybutyrate (BHB) in particular, in reducing NLRP3 inflammasome activation to improve chronic inflammation. As a result, interventions that can induce ketosis (e.g., fasting, intermittent fasting, time-restricted feeding/eating, very low-carbohydrate high-fat ketogenic diets) and/or increase circulating BHB (e.g., exogenous ketone supplementation) have garnered increasing interest for their therapeutic potential. The purpose of the present review is to summarize our current understanding of the literature on how ketogenic interventions impact the NLRP3 inflammasome across human, rodent and cell models. Overall, there is convincing evidence that ketogenic interventions, likely acting through multiple interacting mechanisms in a cell-, disease- and context-specific manner, can reduce NLRP3 inflammasome activation. The evidence supports a direct effect of BHB, although it is important to consider the myriad of other metabolic responses to fasting or ketogenic diet interventions (e.g., elevated lipolysis, low insulin, stable glucose, negative energy balance) that may also impact innate immune responses. Future research is needed to translate promising findings from discovery science to clinical application.
摘要：
NLRP3炎症小体的过度激活与各种疾病状态相关的慢性低度炎症有关。包括肥胖,2型糖尿病,动脉粥样硬化,老年痴呆症,和帕金森病。新出现的证据,主要来自疾病的细胞和动物模型，一般支持酮症的作用，特别是主要的循环酮体β-羟基丁酸酯（BHB），减少NLRP3炎性体激活以改善慢性炎症。因此,可以诱发酮症的干预措施(例如，禁食,间歇性禁食,限时喂养/进食，极低碳水化合物高脂肪生酮饮食)和/或增加循环BHB(例如，外源性酮补充）对其治疗潜力越来越感兴趣。本综述的目的是总结我们目前对生酮干预如何影响NLRP3炎症小体的文献的理解。啮齿动物和细胞模型。总的来说,有令人信服的证据表明生酮干预，可能通过细胞中的多种相互作用机制发挥作用-，疾病和上下文特定的方式，可以降低NLRP3炎性体的激活。证据支持BHB的直接作用，尽管重要的是要考虑对禁食或生酮饮食干预的无数其他代谢反应(例如，脂肪分解升高,低胰岛素，稳定的葡萄糖，负能量平衡)，也可能影响先天免疫反应。未来的研究需要将有希望的发现从发现科学转化为临床应用。
