Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2

Yi Wang, Yuanyuan Qian, Qilu Fang, Peng Zhong, Weixin Li, Lintao Wang, Weitao Fu, Yali Zhang, Zheng Xu, Xiaokun Li and Guang Liang ()
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Yi Wang: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Yuanyuan Qian: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Qilu Fang: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Peng Zhong: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Weixin Li: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Lintao Wang: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Weitao Fu: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Yali Zhang: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Zheng Xu: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Xiaokun Li: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University
Guang Liang: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Obesity increases the risk for a number of diseases including cardiovascular diseases and type 2 diabetes. Excess saturated fatty acids (SFAs) in obesity play a significant role in cardiovascular diseases by activating innate immunity responses. However, the mechanisms by which SFAs activate the innate immune system are not fully known. Here we report that palmitic acid (PA), the most abundant circulating SFA, induces myocardial inflammatory injury through the Toll-like receptor 4 (TLR4) accessory protein MD2 in mouse and cell culture experimental models. Md2 knockout mice are protected against PA- and high-fat diet-induced myocardial injury. Studies of cell surface binding, cell-free protein–protein interactions and molecular docking simulations indicate that PA directly binds to MD2, supporting a mechanism by which PA activates TLR4 and downstream inflammatory responses. We conclude that PA is a crucial contributor to obesity-associated myocardial injury, which is likely regulated via its direct binding to MD2.

Date: 2017
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DOI: 10.1038/ncomms13997

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