Dysregulation of Components of the Inflammasome Machinery After Bariatric Surgery: Novel Targets for a Chronic Disease
| Autor: | Juan L López-Cánovas, Prudencio Sáez-Martínez, Fernando L.‐ López, Elena M. Yubero-Serrano, Aura D. Herrera-Martínez, Justo P. Castaño, Raúl M. Luque, Rosario Alonso-Echague, Maria Dolores Alcantara-Laguna, Alfonso Calañas-Continente, Juan Castilla, María A Gálvez-Moreno, María J. Molina-Puerta, Juan J Prados-Carmona, Manuel D. Gahete, Juan Ruiz-Ravelo, Vicente Herrero-Aguayo, Antonio Membrives |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Sleeve gastrectomy medicine.medical_specialty Chemokine Inflammasomes Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Bariatric Surgery Type 2 diabetes Biochemistry Pyrin domain Cohort Studies Chemokine receptor AIM2 Endocrinology NLRC4 Gastrectomy medicine Humans Dyslipidemias Inflammation biology business.industry Biochemistry (medical) Inflammasome Middle Aged medicine.disease Prognosis Surgery Obesity Morbid Diabetes Mellitus Type 2 Chronic Disease biology.protein Leukocytes Mononuclear Female Inflammation Mediators business Biomarkers medicine.drug Follow-Up Studies |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 106(12) |
| ISSN: | 1945-7197 |
| Popis: | 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. 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). 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. |
| Databáze: | OpenAIRE |
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