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Sphingolipid metabolism during TLR4-mediated macrophage activation

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Title: Sphingolipid metabolism during TLR4-mediated macrophage activation
Authors: Behmoaras, J
Item Type: Journal Article
Abstract: Macrophage activation in response to stimulation of Toll-like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulate the inflammatory response. TLR4-mediated pro-inflammatory macrophage activation is characterised by increased glycolysis and altered mitochondrial metabolism, supported by selective amino acid uptake and/or usage. Fatty acid metabolism remains as a highly complex rewiring that accompany classical macrophage activation. TLR4 activation leads to de novo synthesis of fatty acids, which flux into sphingolipids, complex lipids that form the building blocks of eukaryotic cell membranes and regulate cell function. Here we review the importance of TLR4-mediated de novo synthesis of membrane sphingolipids in macrophages. We first highlight fatty acid metabolism during TLR4-driven macrophage immunometabolism. We then focus on the temporal dynamics of sphingolipid biosynthesis and emphasise the modulatory role of some sphingolipid species (i.e. sphingomyelins, ceramides and glycosphingolipids) on the pro-inflammatory and pro-resolution phases of LPS/TLR4 activation in macrophages.
Issue Date: 6-Aug-2021
Date of Acceptance: 27-Jul-2021
URI: http://hdl.handle.net/10044/1/90940
DOI: 10.1111/bph.15642
ISSN: 0007-1188
Publisher: Wiley
Journal / Book Title: British Journal of Pharmacology
Copyright Statement: This article is protected by copyright. All rights reserved. This is the accepted version of the following article: Olona, A, Hateley, C, Muralidharan, S, Wenk, MR, Torta, F, Behmoaras, J. Sphingolipid metabolism during TLR4-mediated macrophage activation. Br J Pharmacol. 2021. Accepted Author Manuscript, which has been published in final form at https://doi.org/10.1111/bph.15642
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/N01121X/1
EP/V520354/1
Keywords: Pharmacology & Pharmacy
1115 Pharmacology and Pharmaceutical Sciences
Publication Status: Published online
Embargo Date: 2022-08-05
Online Publication Date: 2021-08-06
Appears in Collections:Department of Immunology and Inflammation