Adipocyte-derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance

作者：Zhang, Song-Yang; Dong, Yong-Qiang; Wang, Pengcheng; Zhang, Xingzhong; Yan, Yu; Sun, Lulu; Liu, Bo; Zhang, Dafang; Zhang, Heng; Liu, Huiying; Kong, Wei; Hu, Gang; Shah, Yatrik M.; Gonzalez, Frank J.; Wang, Xian^*; Jiang, Changtao^*

来源：EBioMedicine, 2018, 31: 202-216.

DOI：10.1016/j.ebiom.2018.04.022

• Insulin resistance
• NLRP3 inflammasome
• Homocysteine
• Adipocyte
• Adipose tissue macrophage

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(Hill)-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.

• 出版日期2018-5
• 单位南京医科大学; 北京大学; 首都医科大学; 南京中医药大学