NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction Pavillard, Luís E. Quiles Morales, José Luis NLRP3-inflammasome Cardiac damage Autophagy MCC950 The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases. 2020-12-17T07:57:24Z 2020-12-17T07:57:24Z 2017-09-08 info:eu-repo/semantics/article Pavillard L. E., Cañadas-Lozano D., Alcocer-Gómez E., Marín-Aguilar F., Pereira S., Robertson A. A.B., Muntané J., Ryffel B., Cooper M. A., Quiles J. L., Bullón P., Ruiz-Cabello J., Cordero M. D. et al NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction. Oncotarget. 2017; 8: 99740-99756 [https://doi.org/10.18632/oncotarget.20763] http://hdl.handle.net/10481/64964 10.18632/oncotarget.20763 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España Impact Journals