NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity. (11th October 2019)

• Record Type: Journal Article
• Authors: Marín-Aguilar, Fabiola; Castejón-Vega, Beatriz; Alcocer-Gómez, Elísabet; Lendines-Cordero, Debora; Cooper, Matthew A; de la Cruz, Patricia; Andújar-Pulido, Eloísa; Pérez-Alegre, Mónica; Muntané, Jordi; Pérez-Pulido, Antonio J; Ryffel, Bernhard; Robertson, Avril A B; Ruiz-Cabello, Jesús; Bullón, Pedro; Cordero, Mario D
• Editors: Anderson, Rozalyn
• Is Part Of: Journals of gerontology. Volume 75:Number 8(2020)
• Page Start: 1457
• Page End: 1464
• Publication Date: 2019-10-11
• Subjects: NLRP3 inflammasome -- Aging -- Autophagy -- MCC950 -- PPARα; Geriatrics -- Periodicals; Gerontology -- Periodicals; 618.97
• DOI: 10.1093/gerona/glz239
• Languages: English
• ISSNs: 1079-5006

Abstract

Abstract: 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.