1. NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity.
- Author
-
Marín-Aguilar F, Castejón-Vega B, Alcocer-Gómez E, Lendines-Cordero D, Cooper MA, de la Cruz P, Andújar-Pulido E, Pérez-Alegre M, Muntané J, Pérez-Pulido AJ, Ryffel B, Robertson AAB, Ruiz-Cabello J, Bullón P, and Cordero MD
- Subjects
- Aging, Animals, Fatty Liver prevention & control, Furans, Gene Expression, Indenes, Lipids blood, Liver metabolism, Mice, Inbred C57BL, Proto-Oncogene Proteins c-akt drug effects, Sulfonamides, TOR Serine-Threonine Kinases drug effects, Autophagy drug effects, Heterocyclic Compounds, 4 or More Rings pharmacology, Inflammasomes antagonists & inhibitors, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, PPAR alpha drug effects, Sulfones pharmacology
- 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., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF