Extracellular inflammasome particles promote visceral adipose tissue inflammation

Abstract Background The metabolic syndrome is characterized by a chronic low-grade inflammation that increases the risk for cardiovascular events. With its capability to activate IL-1β, the NLRP3-inflammasome is believed to affect the inflammatory process. When the inflammasome is primed and activated, cytosolic ASC aggregates into the ASC-speck. This inflammasome particle can persist in the extracellular space after the cell it originated from underwent pyroptosis. Purpose We aimed to assess the role of extracellular inflammasome particles as a potential target to reduce chronic inflammation in the metabolic syndrome. Methods Male C57BL6/J mice received either a chow or high-fat-diet (HFD) for 7, 14 or 21 weeks. Flow cytometry and fluorescence microscopy were used to detect inflammasome particles. Adipocytes and stromal vascular fraction (SVF) were isolated from subcutaneous (scWAT) and visceral white adipose tissue (vWAT) using collagenase. Results Mice subjected to HFD show increased NLRP3-inflammasome priming in the SVF of visceral but not subcutaneous WAT (vWAT: 4-fold p