HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation

Xanthe A.M.H. van Dierendonck; Montserrat A. de la Rosa Rodriguez; Anastasia Georgiadi; Frits Mattijssen; Wieneke Dijk; Michel van Weeghel; Rajat Singh; Jan Willem Borst; Rinke Stienstra; Sander Kersten

doi:10.1016/j.celrep.2020.01.046

HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation

Xanthe A.M.H. van Dierendonck, Montserrat A. de la Rosa Rodriguez, Anastasia Georgiadi, Frits Mattijssen, Wieneke Dijk, Michel van Weeghel, Rajat Singh, Jan Willem Borst, Rinke Stienstra, Sander Kersten

Medicine

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19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1811-1822.e6
Journal	Cell Reports
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2020.01.046
State	Published - Feb 11 2020

Keywords

ATGL
Hilpda
fatty acid metabolism
inflammation
lipid droplets
macrophages
obesity

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2020.01.046

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van Dierendonck, X. A. M. H., de la Rosa Rodriguez, M. A., Georgiadi, A., Mattijssen, F., Dijk, W., van Weeghel, M., Singh, R., Borst, J. W., Stienstra, R., & Kersten, S. (2020). HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation. Cell Reports, 30(6), 1811-1822.e6. https://doi.org/10.1016/j.celrep.2020.01.046

HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation. / van Dierendonck, Xanthe A.M.H.; de la Rosa Rodriguez, Montserrat A.; Georgiadi, Anastasia; Mattijssen, Frits; Dijk, Wieneke; van Weeghel, Michel; Singh, Rajat; Borst, Jan Willem; Stienstra, Rinke; Kersten, Sander.

In: Cell Reports, Vol. 30, No. 6, 11.02.2020, p. 1811-1822.e6.

Research output: Contribution to journal › Article › peer-review

van Dierendonck, XAMH, de la Rosa Rodriguez, MA, Georgiadi, A, Mattijssen, F, Dijk, W, van Weeghel, M, Singh, R, Borst, JW, Stienstra, R & Kersten, S 2020, 'HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation', Cell Reports, vol. 30, no. 6, pp. 1811-1822.e6. https://doi.org/10.1016/j.celrep.2020.01.046

van Dierendonck, Xanthe A.M.H. ; de la Rosa Rodriguez, Montserrat A. ; Georgiadi, Anastasia ; Mattijssen, Frits ; Dijk, Wieneke ; van Weeghel, Michel ; Singh, Rajat ; Borst, Jan Willem ; Stienstra, Rinke ; Kersten, Sander. / HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation. In: Cell Reports. 2020 ; Vol. 30, No. 6. pp. 1811-1822.e6.

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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 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",

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T1 - HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation

AU - van Dierendonck, Xanthe A.M.H.

AU - de la Rosa Rodriguez, Montserrat A.

AU - Georgiadi, Anastasia

AU - Mattijssen, Frits

AU - Dijk, Wieneke

AU - van Weeghel, Michel

AU - Singh, Rajat

AU - Borst, Jan Willem

AU - Stienstra, Rinke

AU - Kersten, Sander

N1 - 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: © 2020 The Author(s)

PY - 2020/2/11

Y1 - 2020/2/11

N2 - 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.

AB - 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.

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KW - lipid droplets

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HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation

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