by 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, Jesus, Bullón, Pedro and Cordero, Mario D
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-$alpha$ 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-$alpha$. 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.
Reference:
NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPAR$alpha$ Activity. (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, Jesus, Bullón, Pedro and Cordero, Mario D), In The journals of gerontology. Series A, Biological sciences and medical sciences, volume 75, 2020.
Bibtex Entry:
@article{MarinAguilar:2020kv, author = {Mar{'i}n-Aguilar, Fabiola and Castej{'o}n-Vega, Beatriz and Alcocer-G{'o}mez, El{'i}sabet and Lendines-Cordero, Debora and Cooper, Matthew A and de la Cruz, Patricia and And{'u}jar-Pulido, Elo{'i}sa and P{'e}rez-Alegre, M{'o}nica and Muntan{'e}, Jordi and P{'e}rez-Pulido, Antonio J and Ryffel, Bernhard and Robertson, Avril A B and Ruiz-Cabello, Jesus and Bull{'o}n, Pedro and Cordero, Mario D}, title = {{NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPAR$alpha$ Activity.}}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, year = {2020}, volume = {75}, number = {8}, pages = {1457--1464}, month = jul, affiliation = {Research Laboratory, Oral Medicine Department, University of Sevilla, Seville, Spain.}, doi = {10.1093/gerona/glz239}, pmid = {31603987}, language = {English}, rating = {0}, date-added = {2020-10-13T14:50:09GMT}, date-modified = {2020-10-13T14:59:32GMT}, 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-$alpha$ 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-$alpha$. 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.}, url = {https://academic.oup.com/biomedgerontology/article/75/8/1457/5585925}, uri = {url{papers3://publication/doi/10.1093/gerona/glz239}} }