Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8437322 | EBioMedicine | 2018 | 15 Pages |
Abstract
The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation. Hcy elevated adipocyte lyso-PC generation in a hypoxia-inducible factor 1 (HIF1)-phospholipase A2 group 16 (PLA2G16) axis-dependent manner. Lyso-PC derived from the Hcy-induced adipocyte also activated ATM NLRP3 inflammasomes in a paracrine manner. This study demonstrated that Hcy activates adipose NLRP3 inflammasomes in an adipocyte lyso-PC-dependent manner and highlights the importance of the adipocyte NLRP3 inflammasome in insulin resistance.
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Authors
Song-Yang Zhang, Yong-Qiang Dong, Pengcheng Wang, Xingzhong Zhang, Yu Yan, Lulu Sun, Bo Liu, Dafang Zhang, Heng Zhang, Huiying Liu, Wei Kong, Gang Hu, Yatrik M. Shah, Frank J. Gonzalez, Xian Wang, Changtao Jiang,