Abstract
The Nod-like receptor protein 3 (NLRP3) inflammasome is considered to be a pivotal host platform responsible for sensing of exogenous and endogenous danger signals, including those generated as a result of metabolic dysregulation, and for the subsequent, IL-1β-mediated orchestration of inflammatory and innate immunity responses. In this way, although the molecular link between diet-induced obesity and inflammasome activation is still unclear, free fatty acids (FFA) have been proposed as a triggering event. We report that dietary fatty acid (FA) composition is sensed by the NLRP3 inflammasome in human macrophages. For this purpose, we have analysed three roles of FA supplementation: as a priming signal for ATP-activated macrophages, in determining where the administration of dietary FAs interferes with LPS-mediated inflammasome activation and by inducing inflammasome activation per se. In this study, we confirm that saturated (SFAs) activated the NLRP3 inflammasome and stimulated the secretion of the IL-1β cytokine, while PUFAs were mainly inhibitors. Moreover, in general, DHA (n-3 PUFA) was more effective in preventing inflammasome activation than arachidonic acid (n-6 PUFA).
Highlights
Immunity and metabolism are considered fundamental systems for survival
fatty acid (FA) modulate the activation of the nuclear factor κB (NF-κB) pathway in human macrophages differentially
To determine whether the FA composition of a diet might have a crucial role in macrophage inflammasome activation, modulation of the NF-κB signalling pathway was first analysed
Summary
Immunity and metabolism are considered fundamental systems for survival. Tissues and blood FA are mainly derived from the diet and have been used as dietary intake biomarkers.[2] FAs present in the diet can be divided into two major classes depending on their degree of saturation: saturated (SFAs) or unsaturated fatty acids (UFAs). Palmitate (16:0) and stearate (18:0) are the most important SFAs in the blood, representing 90% of the total SFAs.[2] UFAs can be divided into monounsaturated and polyunsaturated FAs (MUFAs and PUFAs, respectively), and PUFAs are further divided into two categories, namely, omega-6 and omega-3, based on the location of the first double bond of the FA molecule. Arachidonic acid (C20:4 n-6) and docosahexaenoic acid (DHA, C22:6 n-3) are both considered to be key FAs because the omega-6/omega-3 ratio is directly related to the pathogenesis of many diseases, includ-
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