RT Journal Article
T1 Dysregulation of Components of the Inflammasome Machinery After Bariatric Surgery: Novel Targets for a Chronic Disease
A1 Herrero-Aguayo, Vicente
A1 Saez-Martinez, Prudencio
A1 Lopez-Canovas, Juan L.
A1 Prados-Carmona, Juan J.
A1 Alcantara-Laguna, Maria D.
A1 Lopez, Fernando L.
A1 Molina-Puerta, Maria J.
A1 Calanas-Continente, Alfonso
A1 Membrives, Antonio
A1 Castilla, Juan
A1 Ruiz-Ravelo, Juan
A1 Alonso-Echague, Rosario
A1 Yubero-Serrano, Elena M.
A1 Castano, Justo P.
A1 Gahete, Manuel D.
A1 Galvez-Moreno, Maria A.
A1 Luque, Raul M.
A1 Herrera-Martinez, Aura D.
K1 obesity
K1 bariatric surgery
K1 inflammasome
K1 evolution
K1 comorbidities
K1 Subcutaneous adipose-tissue
K1 Fatty liver-disease
K1 Weight-loss
K1 Gut microbiota
K1 Obesity
K1 Mechanisms
K1 Expression
K1 Interleukin-6
K1 Activation
K1 Biguanides
AB 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 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.
PB Endocrine soc
SN 0021-972X
YR 2021
FD 2021-08-07
LK https://hdl.handle.net/10668/25888
UL https://hdl.handle.net/10668/25888
LA en
DS RISalud
RD Apr 7, 2025