Oncotarget

Research Papers:

NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction

Luís E. Pavillard, Diego Cañadas-Lozano, Elísabet Alcocer-Gómez, Fabiola Marín-Aguilar, Sheila Pereira, Avril A.B. Robertson, Jordi Muntané, Bernhard Ryffel, Matthew A. Cooper, José L. Quiles, Pedro Bullón, Jesús Ruiz-Cabello and Mario D. Cordero _

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Oncotarget. 2017; 8:99740-99756. https://doi.org/10.18632/oncotarget.20763

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Abstract

Luís E. Pavillard1,*, Diego Cañadas-Lozano1,*, Elísabet Alcocer-Gómez1, Fabiola Marín-Aguilar1, Sheila Pereira2, Avril A.B. Robertson3, Jordi Muntané4,7, Bernhard Ryffel5, Matthew A. Cooper3, José L. Quiles8, Pedro Bullón1,**, Jesús Ruiz-Cabello6,** and Mario D. Cordero8,**

1Research Laboratory, Oral Medicine Department, University of Sevilla, Sevilla, Spain

2Institute of Biomedicine of Seville (IBiS), “Virgen del Rocío” University Hospital, IBiS, CSIC, University of Seville, Seville, Spain

3Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

4Department of General Surgery, Hospital Universitario Virgen del Rocio, CSIC, Universidad de Sevilla, Sevilla, Spain

5University and CNRS, UMR7355, Orléans, France

6CIBER de Enfermedades Respiratorias, Madrid, Spain; Advanced Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares, and Universidad Complutense Madrid, Madrid, Spain

7Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD o Ciberehd), Instituto de Salud Carlos III, Madrid, Spain

8Institute of Nutrition and Food Technology “José Mataix Verdú”, Department of Physiology, Biomedical Research Center, University of Granada, Granada, Spain

*These authors have contributed equally to this work

**Co-senior author

Correspondence to:

Mario D. Cordero, email: [email protected]

Keywords: NLRP3-inflammasome, cardiac damage, autophagy, MCC950

Received: June 28, 2017     Accepted: July 29, 2017     Published: September 08, 2017

ABSTRACT

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.


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