Triglyceride Breakdown from Lipid Droplets Regulates the Inflammatory Response in Macrophages

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 18

PMID 35302892

Authors

Xanthe A M H van Dierendonck

Frank Vrieling

Lisa Smeehuijzen

Lei Deng

Joline P Boogaard

Cresci-Anne Croes

Lieve Temmerman

Suzan Wetzels

Erik Biessen

Sander Kersten

Rinke Stienstra

Affiliations

Soon will be listed here.

Abstract

In response to inflammatory activation by pathogens, macrophages accumulate triglycerides in intracellular lipid droplets. The mechanisms underlying triglyceride accumulation and its exact role in the inflammatory response of macrophages are not fully understood. Here, we aim to further elucidate the mechanism and function of triglyceride accumulation in the inflammatory response of activated macrophages. Lipopolysaccharide (LPS)-mediated activation markedly increased triglyceride accumulation in macrophages. This increase could be attributed to up-regulation of the hypoxia-inducible lipid droplet–associated (HILPDA) protein, which down-regulated adipose triglyceride lipase (ATGL) protein levels, in turn leading to decreased ATGL-mediated triglyceride hydrolysis. The reduction in ATGL-mediated lipolysis attenuated the inflammatory response in macrophages after ex vivo and in vitro activation, and was accompanied by decreased production of prostaglandin-E2 (PGE2) and interleukin-6 (IL-6). Overall, we provide evidence that LPS-mediated activation of macrophages suppresses lipolysis via induction of HILPDA, thereby reducing the availability of proinflammatory lipid precursors and suppressing the production of PGE2 and IL-6.

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