Dysregulation of components of the inflammasome machinery after bariatric surgery: novel targets for a chronic disease

Background Obesity is a metabolic-chronic disease with important associated morbidities and mortality. Bariatric-surgery is the most effective treatment for maintaining long-term weight-loss in severe obesity and consequently for decreasing obesity-related complications, including chronic inflammation. Aim To explore changes in components of the inflammasome-machinery after bariatric-surgery and their relations with clinical/biochemical-parameters at baseline and six-months after bariatric-surgery. Patients and methods 22 patients with morbid-obesity that underwent bariatric-surgery (sleeve-gastrectomy and roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and six-months after bariatric-surgery. Inflammasome-components and inflammatory-associated factors [NOD-like-receptors (NLRs); inflammasome-activation-components; cytokines and inflammation/apoptosis-related components; and cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs) at baseline and six-months after bariatric-surgery. Clinical-molecular correlations/associations were analyzed. Functional parameters (lipid-accumulation/viability/apoptosis) were analyzed in response to specific inflammasome-components silencing in liver HEPG2-cells-). Results A profound dysregulation of inflammasome-components after bariatric-surgery was found, especially in NOD-like-receptors, cell-cycle and DNA-damage regulators. Several components were associated to baseline metabolic comorbidities including type-2-diabetes (CCL2/CXCR1/SIRT1), hypertension (AIM2/ASC/P2RX7) and dyslipidemia (CXCL3/NLRP7), and displayed changes in their molecular profile six-months after bariatric-surgery. Gene-expression fingerprint of certain factors (NLRC4/NLRP12/CXCL3/CCL8/TLR4) accurately differentiated pre- and post-operative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12- resulted in altered lipid-accumulation, apoptosis-rate and cell-viability in HEPG2-cells. Conclusion Bariatric-surgery induces a profound alteration in gene-expression pattern of components of the inflammasome-machinery in PBMCs. Expression and changes of certain inflammasome-components are associated to baseline metabolic comorbidities, including type-2-diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric-surgery.