NLRP3‐Caspase‐1 Axis in Human Adipose Tissue Crown‐Like Structures: A Potential Mediator of Inflammation and the Effects of Bariatric Surgery

BACKGROUND: Obesity-related comorbidities, such as type 2 diabetes, are associated with chronic inflammation mediated by macrophages. This inflammation is characterized by the accumulation of macrophages in crown-like structures (CLS) surrounding dead adipocytes within adipose tissue. In a recent study, we reported a significant reduction in CLS-associated macrophages following bariatric surgery. The NLRP3 inflammasome and its downstream effector, Caspase-1, are well-established mediators of metabolic dysfunction and inflammation in obesity. METHODS: Immunohistochemical single- and multiplex staining of subcutaneous adipose tissue (SAT) samples from patients with obesity was performed to characterize the detailed distribution of NLRP3 and Caspase-1. The samples were collected during gastric bypass surgery and at a 1-year follow-up. RESULTS: Both NLRP3 and Caspase-1 were expressed by CD68-positive macrophages in SAT including both single macrophages and those forming CLS. A reduction in the total number of SAT macrophages expressing these proteins was detected following gastric bypass. Furthermore, NLRP3 and Caspse-1 were observed in the endothelium of vascular structures. CONCLUSIONS: Our findings demonstrate that both CLS-forming and single cell macrophage populations in human adipose tissue express NLRP3 and Caspase-1. The study highlights the significance of the NLRP3 inflammasome macrophages in the pathogenesis of adipose tissue inflammation in obesity. The previously reported abundance of CLS in untreated obesity and their reduction after bariatric surgery suggest that the NLRP3-Caspase-1 axis within CLS may serve as an important mediator of the beneficial metabolic effects associated with bariatric surgery.