Project description: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.
Project description:The goal of this study was to compare the transcriptional responses of mouse macrophages treated with unsaturated or saturated fatty acids to macrophages treated with LPS to stimulate classical inflammatory activation. Microarray profiling was performed on total RNA isolated from primary mouse bone marrow-derived macrophages (BMDMs) treated with fatty acids (C18:1 oleic acid or C18:0 stearic acid), BSA vehicle, or LPS at two time points.
