Sphingolipid metabolism during Toll‐like receptor 4 (TLR4)‐mediated macrophage activation. (2nd September 2021)

• Record Type: Journal Article
• Authors: Olona, Antoni; Hateley, Charlotte; Muralidharan, Sneha; Wenk, Markus R.; Torta, Federico; Behmoaras, Jacques
• Is Part Of: British journal of pharmacology. Volume 178:Number 23(2021)
• Page Start: 4575
• Page End: 4587
• Publication Date: 2021-09-02
• Subjects: fatty acid metabolism -- lipidomics -- LPS -- macrophages -- sphingolipids -- TLR4; Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.15642
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : Macrophage activation in response to stimulation of Toll‐like receptor 4 (TLR4) provides a paradigm for investigating energy metabolism that regulates the inflammatory response. TLR4‐mediated pro‐inflammatory macrophage activation is characterized 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 accompanies 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 emphasize 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.