Triglyceride breakdown from lipid droplets regulates the inflammatory response in macrophages

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

41 Citations (Scopus)


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.

Original languageEnglish
Article numbere2114739119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
Publication statusPublished - 18 Mar 2022


  • ATGL
  • Immunometabolism
  • Lipid droplets
  • Macrophages


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