Neudorf Helena, Jackson Garett, Little Jonathan P
School of Health and Exercise Sciences, University of British Columbia, Okanagan Campus, Kelowna V1V 1V7, Canada.
J Nutr Metab. 2022 Apr 6;2022:7672759. doi: 10.1155/2022/7672759. eCollection 2022.
Chronic, low-grade inflammation is associated with the development of numerous diseases and is mediated in part by overactivation of the NLRP3 inflammasome. The ketone body beta-hydroxybutyrate (HB) suppresses the NLRP3 inflammasome and alters intracellular signalling pathways in vitro and in animal models; however, this effect has not yet been shown in vivo in humans. The purpose of this single-arm pilot trial was to determine if consuming 15 mL of C medium-chain triglyceride (trioctanoin; MCT) oil, which induces mild elevation of HB, twice daily (30 mL total) for 14 days would suppress markers of NLRP3 inflammasome activation in young, healthy humans while following their habitual diet. Consuming a single dose of 15 mL of C MCT oil significantly raised blood HB from fasting at 60 minutes and 120 minutes post ingestion (both < 0.05). However, consumption of C MCT oil for 14 days did not impact markers of monocyte NLRP3 inflammasome activation compared to baseline. Specifically, caspase-1 activation and secretion of its downstream product interleukin (IL)-1 were unchanged following 14 days of C MCT oil supplementation when measured in unstimulated and LPS-stimulated whole blood cultures (all > 0.05). Acetylation of histone H3 on the lysine residue 9 was unchanged ( < 0.05) and acetylation of lysine residue 14 was decreased ( < 0.05) following 14 days of supplementation. Thus, adding twice daily C MCT oil supplementation to the habitual diet of young, healthy humans does not appear to suppress NLRP3 inflammasome activation.
慢性低度炎症与多种疾病的发生有关，部分是由NLRP3炎性小体的过度激活介导的。酮体β-羟基丁酸酯（HB）在体外和动物模型中可抑制NLRP3炎性小体并改变细胞内信号通路；然而，这种作用尚未在人类体内得到证实。这项单臂试验的目的是确定，在年轻健康人群遵循其日常饮食的同时，每天两次（共30 mL）服用15 mL C中链甘油三酯（三辛酸甘油酯；MCT）油，这种油可使HB轻度升高，持续14天，是否会抑制NLRP3炎性小体激活的标志物。单次服用15 mL C MCT油可使血液中的HB在摄入后60分钟和120分钟时显著高于空腹水平（均P<0.05）。然而，与基线相比，连续14天服用C MCT油并未影响单核细胞NLRP3炎性小体激活的标志物。具体而言，在未刺激和脂多糖刺激的全血培养物中测量时，补充C MCT油14天后，半胱天冬酶-1的激活及其下游产物白细胞介素（IL）-1的分泌均未改变（均P>0.05）。补充14天后，赖氨酸残基9上的组蛋白H3乙酰化未改变（P<0.05），而赖氨酸残基14的乙酰化降低（P<0.05）。因此，在年轻健康人群的日常饮食中每天两次补充C MCT油似乎不会抑制NLRP3炎性小体的激活。
