NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction.
NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction.
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DOI：
10.18632/oncotarget.20763
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发表时间：
2017-11-21
期刊：
影响因子：
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通讯作者：
Cordero MD
中科院分区：
文献类型：
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作者：
Pavillard LE;Cañadas-Lozano D;Alcocer-Gómez E;Marín-Aguilar F;Pereira S;Robertson AAB;Muntané J;Ryffel B;Cooper MA;Quiles JL;Bullón P;Ruiz-Cabello J;Cordero MD
NLRP3-炎症体复合体在高热量饮食诱导的代谢功能障碍中是炎症过程的重要组成部分。在这项研究中，我们研究了抑制NLRP3可能减轻饮食诱导的心脏损伤的分子机制。在这里，我们显示了高糖饮食(HSD)、高脂肪饮食(HFD)或高糖/脂肪饮食(HSFD)在15周内引起的心脏损害。NLRP3的基因消融通过自噬诱导和凋亡控制来保护这种损伤。此外，选择性小分子MCC950抑制NLRP3在饮食后的心脏引起类似的自噬诱导和细胞凋亡控制。这些数据在MCC950处理的THP-1细胞中复制，并在添加MCC950小鼠血清的培养液中培养。抑制NLRP3通过肥胖饮食在心脏中发挥有益的代谢和自噬适应作用。抑制NLRP3的激活有望在代谢和心血管疾病的治疗中发挥作用。
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.