Herrero-Aguayo, VicenteSaez-Martinez, PrudencioLopez-Canovas, Juan L.Prados-Carmona, Juan J.Alcantara-Laguna, Maria D.Lopez, Fernando L.Molina-Puerta, Maria J.Calanas-Continente, AlfonsoMembrives, AntonioCastilla, JuanRuiz-Ravelo, JuanAlonso-Echague, RosarioYubero-Serrano, Elena M.Castano, Justo P.Gahete, Manuel D.Galvez-Moreno, Maria A.Luque, Raul M.Herrera-Martinez, Aura D.2025-01-072025-01-072021-08-070021-972Xhttps://hdl.handle.net/10668/25888Background: 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 relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery.Patients and methods: Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. pidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors [nucleotide-binding oligomerization domain-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 6 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 NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia [C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative 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 the 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.enobesitybariatric surgeryinflammasomeevolutioncomorbiditiesSubcutaneous adipose-tissueFatty liver-diseaseWeight-lossGut microbiotaObesityMechanismsExpressionInterleukin-6ActivationBiguanidesresearch article34363480open access10.1210/clinem/dgab5861945-7197https://doi.org/10.1210/clinem/dgab586744541300009