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J Biol Chem. 2010 Dec 17;285(51):39976-85. doi: 10.1074/jbc.M110.182915. Epub 2010 Oct 5.

A mouse macrophage lipidome.

Author information

1
Department of Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. edennis@ucsd.edu

Abstract

We report the lipidomic response of the murine macrophage RAW cell line to Kdo(2)-lipid A, the active component of an inflammatory lipopolysaccharide functioning as a selective TLR4 agonist and compactin, a statin inhibitor of cholesterol biosynthesis. Analyses of lipid molecular species by dynamic quantitative mass spectrometry and concomitant transcriptomic measurements define the lipidome and demonstrate immediate responses in fatty acid metabolism represented by increases in eicosanoid synthesis and delayed responses characterized by sphingolipid and sterol biosynthesis. Lipid remodeling of glycerolipids, glycerophospholipids, and prenols also take place, indicating that activation of the innate immune system by inflammatory mediators leads to alterations in a majority of mammalian lipid categories, including unanticipated effects of a statin drug. Our studies provide a systems-level view of lipid metabolism and reveal significant connections between lipid and cell signaling and biochemical pathways that contribute to innate immune responses and to pharmacological perturbations.

PMID:
20923771
PMCID:
PMC3000979
DOI:
10.1074/jbc.M110.182915
[Indexed for MEDLINE]
Free PMC Article

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