Triglyceride breakdown from lipid droplets regulates the inflammatory response in macrophages.

Autor:	van Dierendonck XAMH; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands.; Department of Internal Medicine (463), Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands., Vrieling F; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Smeehuijzen L; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Deng L; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Boogaard JP; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Croes CA; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Temmerman L; Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, 6211LK Maastricht, The Netherlands., Wetzels S; Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, 6211LK Maastricht, The Netherlands., Biessen E; Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, 6211LK Maastricht, The Netherlands.; Institute for Molecular Cardiology, Klinikum Rheinisch Westfälische Technische Hochschule Aachen, Aachen, 52074 Germany., Kersten S; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands., Stienstra R; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, 6708WE Wageningen, The Netherlands.; Department of Internal Medicine (463), Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Mar 22; Vol. 119 (12), pp. e2114739119. Date of Electronic Publication: 2022 Mar 18.
DOI:	10.1073/pnas.2114739119
Abstrakt:	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.
Databáze:	MEDLINE
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