Classical Activation of Macrophages Leads to Lipid Droplet Formation Without de novo Fatty Acid Synthesis.

Frontiers in Immunology
Mauricio Rosas-BallinaDirk Bumann

Abstract

Altered lipid metabolism in macrophages is associated with various important inflammatory conditions. Although lipid metabolism is an important target for therapeutic intervention, the metabolic requirement involved in lipid accumulation during pro-inflammatory activation of macrophages remains incompletely characterized. We show here that macrophage activation with IFNγ results in increased aerobic glycolysis, iNOS-dependent inhibition of respiration, and accumulation of triacylglycerol. Surprisingly, metabolite tracing with 13C-labeled glucose revealed that the glucose contributed to the glycerol groups in triacylglycerol (TAG), rather than to de novo synthesis of fatty acids. This is in stark contrast to the otherwise similar metabolism of cancer cells, and previous results obtained in activated macrophages and dendritic cells. Our results establish a novel metabolic pathway whereby glucose provides glycerol to the headgroup of TAG during classical macrophage activation.

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Citations

Oct 30, 2020·Metabolites·Erika M PalmieriDaniel W McVicar
Aug 19, 2020·Seminars in Cell & Developmental Biology·Bruno ChausseOliver Kann
Jan 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kasparas PetkeviciusAntonio Vidal-Puig
Nov 14, 2020·The FEBS Journal·Kourosh H EbrahimiJames S O McCullagh
Jun 14, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Arpana Singh, Prosenjit Sen

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Datasets Mentioned

BETA
PXD017148

Methods Mentioned

BETA
flow cytometry
FCS
FACS

Software Mentioned

Fiji
FlowJo
GSEA
SafeQuant

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