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bioRxiv · 10.1101/566802

HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation

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.
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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.

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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.. 2019-03-05. HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. https://doi.org/10.1101/566802

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