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标题：The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity
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作者：Helena Neudorf ; Étienne Myette-Côté ; Jonathan P. Little 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2020
卷号：12
期号：3
页码：854-866
DOI：10.3390/nu12030854
出版社：MDPI Publishing
摘要：Activation of the NOD-like receptor pyrin-domain containing 3 (NLRP3) inflammasome is associated with chronic low-grade inflammation in metabolic diseases such as obesity. Mechanistic studies have shown that β-hydroxybutyrate (OHB) attenuates activation of NLRP3, but human data are limited. In a randomized, double-blind, placebo-controlled crossover trial (n = 11) we tested the hypothesis that acutely raising β-OHB by ingestion of exogenous ketones would attenuate NLRP3 activation in humans with obesity. Blood was sampled before and 30 min post-ingestion of a ketone monoester drink ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate, 482 mg/kg body mass) or placebo. A 75 g oral glucose load was then ingested, and a third blood sample was obtained 60 min following glucose ingestion. NLRP3 activation was quantified by assessing monocyte caspase-1 activation and interleukin (IL)-1β secretion in ex vivo lipopolysaccharide (LPS)-stimulated whole-blood cultures. LPS-stimulated caspase-1 activation increased following glucose ingestion (main effect of time; p = 0.032), with no differences between conditions. IL-1β secretion did not differ between conditions but was lower 60 min post-glucose ingestion compared to the fasting baseline (main effect of time, p = 0.014). Plasma IL-1β was detectable in ~80% of samples and showed a decrease from fasting baseline to 60 min in the ketone condition only (condition × time interaction, p = 0.01). In individuals with obesity, an excursion into hyperglycemia following ingestion of a glucose load augments LPS-induced activation of caspase-1 in monocytes with no apparent impact of raising circulating β-OHB concentration via ingestion of exogenous ketones. Exogenous ketone supplementation may impact plasma IL-1β, but these findings require confirmation in studies with larger sample sizes.
关键词：ketones; obesity; immunometabolism; inflammation; caspase-1; inflammasome; beta-hydroxybutyrate; 3-hydroxybutyric Acid; interleukin-1β; NLR family; pyrin domain containing-3 protein ketones ; obesity ; immunometabolism ; inflammation ; caspase-1 ; inflammasome ; beta-hydroxybutyrate ; 3-hydroxybutyric Acid ; interleukin-1β ; NLR family ; pyrin domain containing-3 protein