NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity

作者：Fabiola Marín‐Aguilar, Beatriz Castejón‐Vega, Elísabet Alcocer‐Gómez, Débora Lendines‐Cordero, Matthew A. Cooper, Patricia de la Cruz‐Ojeda, Eloísa Andújar, Mónica Pérez-Alegre, Jordi Muntané, Antonio J. Pérez‐Pulido, Bernhard Ryffel, Avril A. B. Robertson, Jesús Ruı́z-Cabello, Pedro Bullón, Mario D. Cordero · 发表于：The Journals of Gerontology Series A · 年份：2019 · DOI：10.1093/gerona/glz239 · 被引用次数：63 · 研究领域：Autophagy in Disease and Therapy、Inflammasome and immune disorders、Cannabis and Cannabinoid Research

The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-related diseases in NLRP3-deficient mice. In this article, we determine whether, in old mice C57BL6J, the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age-related metabolic syndrome to providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. In addition, MCC950 inhibited the Pi3K/AKT/mTOR pathway, enhanced autophagy, and activated peroxisome proliferator-activated receptor-α in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by the mammalian target of rapamycin inhibition, thus activating autophagy and peroxisome proliferator-activated receptor-α. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-related metabolic syndrome.