Regulation of Nlrp3 inflammasome by dietary metabolites |
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Affiliation: | 1. Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, United States;2. Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, United States |
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Abstract: | The bidirectional communication between innate immune cells and energy metabolism is now widely appreciated to regulate homeostasis as well as chronic diseases that emerge from dysregulated inflammation. Macronutrients-derived from diet or endogenous pathways that generate and divert metabolites into energetic or biosynthetic pathways – regulate the initiation, duration and cessation of the inflammatory response. The NLRP3 inflammasome is an important innate sensor of structurally diverse metabolic damage-associated molecular patterns (DAMPs) that has been implicated in a wide range of inflammatory disorders associated with caloric excess, adiposity and aging. Understanding the regulators of immune-metabolic interactions and their contribution towards chronic disease mechanisms, therefore, has the potential to reduce disease pathology, improve quality of life in elderly and promote the extension of healthspan. Just as specialized subsets of immune cells dampen inflammation through the production of negative regulatory cytokines; specific immunoregulatory metabolites can deactivate inflammasome-mediated immune activation. Here, we highlight the role of energy substrates, alternative fuels and metabolic DAMPs in the regulation of the NLRP3 inflammasome and discuss potential dietary interventions that may impact sterile inflammatory disease. |
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Keywords: | Nlrp3 inflammasome DAMP Metabolite Sterile inflammation Dietary intervention Fatty acids Ketones Macrophage TCA" },{" #name" :" keyword" ," $" :{" id" :" kw0045" }," $$" :[{" #name" :" text" ," _" :" the citric acid cycle ETC" },{" #name" :" keyword" ," $" :{" id" :" kw0055" }," $$" :[{" #name" :" text" ," _" :" electron transport chain BHB" },{" #name" :" keyword" ," $" :{" id" :" kw0065" }," $$" :[{" #name" :" text" ," _" :" beta-hydroxybutyrate DAG" },{" #name" :" keyword" ," $" :{" id" :" kw0075" }," $$" :[{" #name" :" text" ," _" :" diacylglycerides TAG" },{" #name" :" keyword" ," $" :{" id" :" kw0085" }," $$" :[{" #name" :" text" ," _" :" triacylglycerides TLR" },{" #name" :" keyword" ," $" :{" id" :" kw0095" }," $$" :[{" #name" :" text" ," _" :" toll like receptor ROS" },{" #name" :" keyword" ," $" :{" id" :" kw0105" }," $$" :[{" #name" :" text" ," _" :" Reactive Oxygen Species NEFA" },{" #name" :" keyword" ," $" :{" id" :" kw0115" }," $$" :[{" #name" :" text" ," _" :" non-esterified fatty acids ER" },{" #name" :" keyword" ," $" :{" id" :" kw0125" }," $$" :[{" #name" :" text" ," _" :" endoplasmic reticulum CVD" },{" #name" :" keyword" ," $" :{" id" :" kw0135" }," $$" :[{" #name" :" text" ," _" :" cardiovascular disease AT" },{" #name" :" keyword" ," $" :{" id" :" kw0145" }," $$" :[{" #name" :" text" ," _" :" adipose tissue LDL" },{" #name" :" keyword" ," $" :{" id" :" kw0155" }," $$" :[{" #name" :" text" ," _" :" low density lipoprotein HDL" },{" #name" :" keyword" ," $" :{" id" :" kw0165" }," $$" :[{" #name" :" text" ," _" :" high density lipoprotein HMGCR" },{" #name" :" keyword" ," $" :{" id" :" kw0175" }," $$" :[{" #name" :" text" ," _" :" HMG-CoA Reductase Sptlc" },{" #name" :" keyword" ," $" :{" id" :" kw0185" }," $$" :[{" #name" :" text" ," _" :" serine palmitoyltransferase CPT" },{" #name" :" keyword" ," $" :{" id" :" kw0195" }," $$" :[{" #name" :" text" ," _" :" carnitine palmitoyltransferase FAO" },{" #name" :" keyword" ," $" :{" id" :" kw0205" }," $$" :[{" #name" :" text" ," _" :" fatty acid oxidation FABP" },{" #name" :" keyword" ," $" :{" id" :" kw0215" }," $$" :[{" #name" :" text" ," _" :" fatty acid binding proteins GPRs" },{" #name" :" keyword" ," $" :{" id" :" kw0225" }," $$" :[{" #name" :" text" ," _" :" G-protein coupled receptors LPL" },{" #name" :" keyword" ," $" :{" id" :" kw0235" }," $$" :[{" #name" :" text" ," _" :" lipoprotein lipase DAMPS" },{" #name" :" keyword" ," $" :{" id" :" kw0245" }," $$" :[{" #name" :" text" ," _" :" damage associated molecular patterns NLRs" },{" #name" :" keyword" ," $" :{" id" :" kw0255" }," $$" :[{" #name" :" text" ," _" :" nod like receptors |
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