Toll-like receptor-dependent lipid body formation in macrophage foam cell formation

Current Opinion in Lipidology
Giovanna Nicolaou, Clett Erridge

Abstract

The differentiation of macrophages into lipid-laden foam cells is central to the development of atherosclerosis. Traditionally, it has been assumed that the uptake of oxidized low-density lipoprotein by macrophage scavenger receptors is largely responsible for this process. However, in light of recent evidence that these mechanisms may not play as large a role as previously thought, alternative mechanisms of foam cell formation are now being explored. The stimulation of Toll-like receptor (TLR) signalling by bacterial molecules has been shown to promote the accumulation of lipid in macrophages in the form of intracellular inclusions termed 'lipid bodies'. Interactions between TLR-signalling pathways and the liver-X receptor and peroxisome proliferator-activated receptor-γ signalling pathways modulate the formation of lipid bodies in macrophages and thereby cellular accumulation of cholesterol and triglyceride. These pathways appear to involve TLR-mediated regulation of lipid-binding proteins, cellular cholesterol sensors, lipid-body-associated proteins and secreted autocrine factors, but are independent of scavenger receptor or lipoprotein oxidation-dependent pathways. TLR stimulation promotes the accumulation of lipid bodies i...Continue Reading

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