@article{134096a85fd348f38ebfa7761b631e43,
title = "HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation",
abstract = "Obesity leads to a state of chronic, low-grade inflammation that features the accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid-droplet accumulation in the development of obesity-induced adipose-tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages can be rescued by inhibition of adipose triglyceride lipase (ATGL) and is associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency does not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-inducible, physiological inhibitor of ATGL-mediated lipolysis in macrophages and uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.",
keywords = "ATGL, Hilpda, fatty acid metabolism, inflammation, lipid droplets, macrophages, obesity",
author = "{van Dierendonck}, {Xanthe A.M.H.} and {de la Rosa Rodriguez}, {Montserrat A.} and Anastasia Georgiadi and Frits Mattijssen and Wieneke Dijk and {van Weeghel}, Michel and Rajat Singh and Borst, {Jan Willem} and Rinke Stienstra and Sander Kersten",
note = "Funding Information: We would like to thank Shohreh Keshtkar, Karin Mudde, Jenny Jansen, Anneke Hijmans, Tessa de Bie, and Jacqueline Ratter for their technical assistance. This work was financed by grants from the Netherlands Organisation of Scientific Research (2014/12393/ALW), the Dutch Diabetes Foundation (2015.82.1824), and the Netherlands Heart Foundation (ENERGISE grant CVON2014-02). X.A.M.H.v.D. M.A.d.l.R, A.G. F.M. W.D. J.W.B. R. Stienstra, and S.K. conceived and planned the research and experiments. X.A.M.H.v.D. carried out the Hilpda?M? mouse studies. X.A.M.H.v.D. M.A.d.l.R. A.G. F.M. and W.D. performed the experiments and analyzed the data. M.v.W. performed the lipidomics analysis. R. Singh, and J.W.B. contributed to the interpretation of the results. X.A.M.H.v.D. performed the statistical analyses. X.A.M.H.v.D. R. Stienstra, and S.K. wrote the manuscript. All authors provided critical feedback and helped to shape the research, analysis, and manuscript. Co-first author order was determined by contribution. The authors declare no competing interests. Funding Information: We would like to thank Shohreh Keshtkar, Karin Mudde, Jenny Jansen, Anneke Hijmans, Tessa de Bie, and Jacqueline Ratter for their technical assistance. This work was financed by grants from the Netherlands Organisation of Scientific Research ( 2014/12393/ALW ), the Dutch Diabetes Foundation ( 2015.82.1824 ), and the Netherlands Heart Foundation (ENERGISE grant CVON2014-02 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = feb,
day = "11",
doi = "10.1016/j.celrep.2020.01.046",
language = "English (US)",
volume = "30",
pages = "1811--1822.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}