Sirtuin 2 Dysregulates Autophagy in High-Fat-Exposed Immune-Tolerant Macrophages.

摘要: Obesity increases morbidity and resource utilization in sepsis patients. The immune response transitions from an endotoxin-responsive hyper- to endotoxin-tolerant hypo-inflammatory phase. majority of mortality occurs during hypo-inflammation. We reported prolonged hypo-inflammation with increased sirtuin 2 (SIRT2) expression obese-septic mice. effect direct exposure high-fat/free fatty acid (FFA) the role SIRT2 cells transition is not well-understood. Autophagy, a degradation process damaged protein/organelles, dysregulated sepsis. Here, we investigated FFA on autophagy as macrophages hyper-to found, FFA-exposed RAW 264.7 lipopolysaccharide (LPS) stimulation undergo endotoxin-sensitive ("sensitive") followed by endotoxin tolerant ("tolerant") phases; significantly cells. Autophagy proteins LC3b-II, beclin-1 increase FFA-sensitive decrease cells; p62 expressions continue accumulate observed that directly deacetylates α-tubulin impairs clearance. Importantly, find inhibitor AK-7 treatment phase reverses dysregulation improved clearance FFA-tolerant Thus, report impaired autophagosome formation via macrophages.