HILPDA uncouples lipid storage 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:10.1101/566802

HILPDA uncouples lipid storage 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

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

Abstract

Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/566802
State	Published - Mar 5 2019

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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HILPDA uncouples lipid storage 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: Unknown Journal, 05.03.2019.

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

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title = "HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation",

abstract = "Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.",

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",

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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 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2019/3/5

Y1 - 2019/3/5

N2 - Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

AB - Obesity promotes accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency in bone marrow-derived macrophages markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids in lipid droplets. Decreased lipid storage in HILPDA-deficient macrophages could be almost completely rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory or metabolic parameters, despite markedly reducing lipid storage in adipose tissue macrophages. Our data indicate that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Overall, our data question the importance of lipid storage in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

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