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Lipids, inflammasomes, metabolism and disease

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Title: Lipids, inflammasomes, metabolism and disease
Authors: Anand, P
Item Type: Journal Article
Abstract: Inflammasomes are multi‐protein complexes that regulate the cleavage of cysteine protease caspase‐1, secretion of inflammatory cytokines, and induction of inflammatory cell death, pyroptosis. Several members of the nod‐like receptor family assemble inflammasome in response to specific ligands. An exception to this is the NLRP3 inflammasome which is activated by structurally diverse entities. Recent studies have suggested that NLRP3 might be a sensor of cellular homeostasis, and any perturbation in distinct metabolic pathways results in the activation of this inflammasome. Lipid metabolism is exceedingly important in maintaining cellular homeostasis, and it is recognized that cells and tissues undergo extensive lipid remodeling during activation and disease. Some lipids are involved in instigating chronic inflammatory diseases, and new studies have highlighted critical upstream roles for lipids, particularly cholesterol, in regulating inflammasome activation implying key functions for inflammasomes in diseases with defective lipid metabolism. The focus of this review is to highlight how lipids regulate inflammasome activation and how this leads to the progression of inflammatory diseases. The key roles of cholesterol metabolism in the activation of inflammasomes have been comprehensively discussed. Besides, the roles of oxysterols, fatty acids, phospholipids, and lipid second messengers are also summarized in the context of inflammasomes. The overriding theme is that lipid metabolism has numerous but complex functions in inflammasome activation. A detailed understanding of this area will help us develop therapeutic interventions for diseases where dysregulated lipid metabolism is the underlying cause.
Issue Date: 1-Sep-2020
Date of Acceptance: 27-May-2020
URI: http://hdl.handle.net/10044/1/80735
DOI: 10.1111/imr.12891
ISSN: 0105-2896
Publisher: Wiley
Start Page: 108
End Page: 122
Journal / Book Title: Immunological Reviews
Volume: 297
Issue: 1
Copyright Statement: © 2020 The Authors. Immunological Reviews published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/S00968X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
cholesterol
homeostasis
inflammasome
lipids
metabolism
NLRP3
RECEPTOR-MEDIATED ENDOCYTOSIS
CELLULAR CHOLESTEROL ACCUMULATION
NF-KAPPA-B
NLRP3 INFLAMMASOME
AIM2 INFLAMMASOME
ADIPOSE-TISSUE
PHOSPHATIDYLINOSITOL 4-PHOSPHATE
ENDOPLASMIC-RETICULUM
INSULIN-RESISTANCE
BACTERIAL LIGANDS
NLRP3
cholesterol
homeostasis
inflammasome
lipids
metabolism
1107 Immunology
Immunology
Publication Status: Published
Online Publication Date: 2020-06-20
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine