A recent study revealed homeostatic roles for foam cells (a type of macrophage present in atherosclerotic lesions) in lipid metabolism and inflammation. Spann et al. isolated foam cells from a mouse model of hypercholesterolaemia and analysed their transcriptomic and lipidomic profiles. High levels of exogenous cholesterol were shown to skew the cholesterol biosynthetic pathway to the production of desmosterol through downregulation of the enzyme DHCR24. Desmosterol is a liver X receptor (LXR) ligand, and intracellular desmosterol altered LXR- and SREBP (sterol regulatory element binding protein)-dependent fatty acid metabolism in foam cells. Moreover, high desmosterol levels inhibited pro-inflammatory gene expression through both LXR-dependent and LXR-independent mechanisms. These findings may foster the development of new therapies against cardiovascular disease.
ORIGINAL RESEARCH PAPER
Spann, N. J. et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151, 138–152 (2012)
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Papatriantafyllou, M. Lipid metabolism linked to anti-inflammatory functions. Nat Rev Immunol 12, 747 (2012). https://doi.org/10.1038/nri3336