PT  - JOURNAL ARTICLE
AU  - Xanthe A.M.H. van Dierendonck
AU  - Montserrat A. de la Rosa Rodriguez
AU  - Anastasia Georgiadi
AU  - Frits Mattijssen
AU  - Wieneke Dijk
AU  - Michel van Weeghel
AU  - Rajat Singh
AU  - Jan Willem Borst
AU  - Rinke Stienstra
AU  - Sander Kersten
TI  - HILPDA uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation
AID  - 10.1101/566802
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 566802
4099  - http://biorxiv.org/content/early/2019/03/05/566802.short
4100  - http://biorxiv.org/content/early/2019/03/05/566802.full
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.