Expression data from cultured mouse macrophages isolated from Hilpdaflox/flox (WT) and HilpdaΔMΦ (KO) mice treated with a mixture of fatty acids

Obesity leads to a state of chronic low-grade inflammation that features 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 could be 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 and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that 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. Bone marrow-derived macrophages (BMDM) isolated from Hilpdaflox/flox (WT) and HilpdaΔMΦ (KO) mice were treated with fatty acids, followed by comparison of the transcriptional profiles. were compared. Microarray profiling was performed on total RNA isolated from mouse bone marrow-derived macrophages treated with 600uM oleate:palmitate mixture (in a ratio of 1:2 palmitate to oleate) for 12 or 24 hours.