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-associated diseases as reported in NLRP3 deficient mice. Here we asked whether in old mice C57BL6J the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age- assocociated metabolic syndrome providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. MCC950 inhibited the Pi3K/AKT/mTOR pathway, and enhanced autophagy and activated peroxisome proliferator-activated receptor alpha (PPAR$alpha$) in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by mTOR inhibiton activating autophagy and PPAR$alpha$. 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-associated 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, 2019.
Bibtex Entry:
@article{MarinAguilar:2019kv,
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 = {2019},
month = oct,
affiliation = {Research Laboratory, Oral Medicine Department, University of Sevilla, Sevilla, Spain.},
doi = {10.1093/gerona/glz239},
pmid = {31603987},
language = {English},
rating = {0},
date-added = {2019-10-18T10:55:26GMT},
date-modified = {2019-10-18T10:56:12GMT},
abstract = {The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-associated diseases as reported in NLRP3 deficient mice. Here we asked whether in old mice C57BL6J the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age- assocociated metabolic syndrome providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. MCC950 inhibited the Pi3K/AKT/mTOR pathway, and enhanced autophagy and activated peroxisome proliferator-activated receptor alpha (PPAR$alpha$) in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by mTOR inhibiton activating autophagy and PPAR$alpha$. 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-associated metabolic syndrome.},
url = {https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glz239/5585925},
uri = {url{papers3://publication/doi/10.1093/gerona/glz239}}
}