%0 Journal Article
%A Herrero-Aguayo, Vicente
%A Sáez-Martínez, Prudencio
%A López-Cánovas, Juan L
%A Prados-Carmona, Juan J
%A Alcántara-Laguna, María D
%A López, Fernando L
%A Molina-Puerta, María J
%A Calañas-Continente, Alfonso
%A Membrives, Antonio
%A Castilla, Juan
%A Ruiz-Ravelo, Juan
%A Alonso-Echague, Rosario
%A Yubero-Serrano, Elena M
%A Castaño, Justo P
%A Gahete, Manuel D
%A Gálvez-Moreno, María A
%A Luque, Raúl M
%A Herrera-Martínez, Aura D
%T Dysregulation of Components of the Inflammasome Machinery After Bariatric Surgery: Novel Targets for a Chronic Disease.
%D 2021
%U https://hdl.handle.net/10668/25887
%X 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. 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. Twenty-two 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 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). 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. 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.
%K bariatric surgery
%K comorbidities
%K evolution
%K inflammasome
%K obesity
%~