Sphingolipid metabolism during TLR4-mediated macrophage activation
File(s)Olona et al (accepted).pdf (497.45 KB)
Accepted version
Author(s)
Behmoaras, J
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.
Date Issued
2021-12
Online Publication Date
2022-08-05T23:01:26Z
Date Acceptance
2021-07-27
ISSN
0007-1188
Publisher
Wiley
Start Page
4575
End Page
4587
Journal / Book Title
British Journal of Pharmacology
Volume
178
Issue
23
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
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.15642
Grant Number
MR/N01121X/1
EP/V520354/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
fatty acid metabolism
lipidomics
LPS
macrophages
sphingolipids
TLR4
FATTY-ACID SYNTHESIS
LIPID RAFTS
GLYCOSPHINGOLIPID METABOLISM
INFLAMMASOME ACTIVATION
RAW264.7 MACROPHAGES
DENDRITIC CELL
LIPOPOLYSACCHARIDE
CERAMIDE
GANGLIOSIDES
LPS
TLR4
fatty acid metabolism
lipidomics
macrophages
sphingolipids
Pharmacology & Pharmacy
1115 Pharmacology and Pharmaceutical Sciences
Publication Status
Published
Date Publish Online
2021-08-06