Increased inflammasome activity in subcutaneous adipose tissue of patients with metabolic syndrome

The metabolic syndrome (MetS) is an inflammatory disorder associated with an increased risk for diabetes and atherosclerotic cardiovascular disease (ASCVD). Studies in patients and animal models of obesity and diabetes have shown increased NOD-like receptor family pyrin domain containing 3 (NLPR3) inflammasome activity. However, there is scanty data on the activity of the NLRP3 inflammasome in patients with nascent MetS. The aim of this study was to determine the status of the inflammasome in subcutaneous adipose tissue (SAT) of patients with nascent MetS without concomitant diabetes, ASCVD and smoking.

Patients with nascent MetS and controls were recruited from Sacramento County. Fasting blood samples were collected for biomediators of inflammation and SAT was obtained by biopsy for immunohistochemical (IHC) staining for caspase 1, IL-1β and IL-18.

Caspase1, a marker of inflammasome activity and its downstream mediators IL-1β and IL-18 were significantly increased in SAT of patients with MetS compared to controls. Significant positive correlations of caspase 1 were obtained with certain cardio-metabolic features, biomediators of inflammation and markers of angiogenesis and fibrosis in SAT. Both mast cell and eosinophil abundance but not macrophage density correlated with caspase1.

We make the novel observation that the SAT of patients with nascent MetS displays increased NLRP3 inflammasome activity manifest by increased caspase 1 in SAT and this may contribute to increased insulin resistance, inflammation and SAT fibrosis in these patients.