炎症体
SIRT2
胰岛素抵抗
炎症
HDAC3型
乙酰化
胰岛素受体
细胞生物学
内分泌学
糖尿病
锡尔图因
免疫学
生物
基因
生物化学
组蛋白脱乙酰基酶
组蛋白
作者
Ming He,Hou-Hsien Chiang,Hanzhi Luo,Zuoping Zheng,Qi Qiao,Li Wang,Mengyao Tan,Rika Ohkubo,Wei‐Chieh Mu,Shimin Zhao,Hao Wu,Danica Chen
出处
期刊:Cell Metabolism
[Elsevier]
日期:2020-03-01
卷期号:31 (3): 580-591.e5
被引量:204
标识
DOI:10.1016/j.cmet.2020.01.009
摘要
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.
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