RT Journal Article
T1 NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction
A1 Pavillard, Luis E.
A1 Canadas-Lozano, Diego
A1 Alcocer-Gomez, Elisabet
A1 Marin-Aguilar, Fabiola
A1 Pereira, Sheila
A1 Robertson, Avril A. B.
A1 Muntane, Jordi
A1 Ryffel, Bernhard
A1 Cooper, Matthew A.
A1 Quiles, Jose L.
A1 Bullon, Pedro
A1 Ruiz-Cabello, Jesus
A1 Cordero, Mario D.
K1 NLRP3-inflammasome
K1 cardiac damage
K1 autophagy
K1 MCC950
K1 Nlrp3 inflammasome activation
K1 Low-grade inflammation
K1 Adipose-tissue
K1 Obesity
K1 Health
K1 Mice
K1 Fibrosis
K1 Disease
K1 Stress
K1 Injury
AB 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.
PB Impact journals llc
YR 2017
FD 2017-11-21
LK http://hdl.handle.net/10668/19443
UL http://hdl.handle.net/10668/19443
LA en
DS RISalud
RD Apr 8, 2025