News

home News

[200410 Àú³Î¹ßÇ¥] An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance

ÇÑÁöÈñ ¦¢ 2020-04-07

HIT

51458

 2020 Mar 3;31(3):580-591.e5. doi: 10.1016/j.cmet.2020.01.009. Epub 2020 Feb 6.

An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance.

Abstract

It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown. Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD+-dependent deacetylase and a metabolic sensor. We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance. These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.

KEYWORDS:

NLRP3; SIRT1; SIRT2; SIRT3; SIRT4; SIRT5; SIRT6; SIRT7; caspase 1; inflammasome

PMID:
 
32032542
 
PMCID:
 
PMC7104778
 [Available on 2021-03-03]
 
DOI:
 
10.1016/j.cmet.2020.01.009




Prev [200402 Àú³Î ¹ßÇ¥] ¥â-Amyloid Clustering around ASC Fibrils Boosts Its Toxicity ...
Next [200410 Àú³Î¹ßÇ¥] Cell-to-cell transmission of C9orf72 poly-(Gly-Ala) triggers k...