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Triacylglycerol synthesis enhances macrophage inflammatory function.

ABSTRACT: Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which prevents LD development, has marked effects on the production of inflammatory mediators, including IL-1?, IL-6 and PGE2, and on phagocytic capacity. The failure of inflammatory macrophages to make PGE2 when TG-synthesis is inhibited is critical for this phenotype, as addition of exogenous PGE2 is able to reverse the anti-inflammatory effects of TG synthesis inhibition. These findings place LDs in a position of central importance in inflammatory macrophage activation.

SUBMITTER: Castoldi A

PROVIDER: S-EPMC7427976 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Triacylglycerol synthesis enhances macrophage inflammatory function.

Castoldi Angela A Monteiro Lauar B LB van Teijlingen Bakker Nikki N Sanin David E DE Rana Nisha N Corrado Mauro M Cameron Alanna M AM Hässler Fabian F Matsushita Mai M Caputa George G Klein Geltink Ramon I RI Büscher Jörg J Edwards-Hicks Joy J Pearce Erika L EL Pearce Edward J EJ

Nature communications 20200814 1

Foamy macrophages, which have prominent lipid droplets (LDs), are found in a variety of disease states. Toll-like receptor agonists drive triacylglycerol (TG)-rich LD development in macrophages. Here we explore the basis and significance of this process. Our findings indicate that LD development is the result of metabolic commitment to TG synthesis on a background of decreased fatty acid oxidation. TG synthesis is essential for optimal inflammatory macrophage activation as its inhibition, which ...[more]

PMID: 32796836

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Dataset Information

Triacylglycerol synthesis enhances macrophage inflammatory function.

Publications

Triacylglycerol synthesis enhances macrophage inflammatory function.

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