Reference - Detail
| RRC ID | 88200 |
|---|---|
| Author | Wang Y, Qian Y, Fang Q, Zhong P, Li W, Wang L, Fu W, Zhang Y, Xu Z, Li X, Liang G. |
| Title | Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2. |
| Journal | Nat Commun |
| 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. |
| Volume | 8 |
| Pages | 13997 |
| Published | 2017-1-3 |
| DOI | 10.1038/ncomms13997 |
| PII | ncomms13997 |
| PMID | 28045026 |
| PMC | PMC5216130 |
| MeSH | Animals Cardiomyopathies / etiology Cardiomyopathies / genetics* Cardiomyopathies / metabolism Cardiomyopathies / pathology Cell Line Diet, High-Fat / adverse effects Gene Expression Regulation Humans Lymphocyte Antigen 96 / chemistry* Lymphocyte Antigen 96 / deficiency Lymphocyte Antigen 96 / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Molecular Docking Simulation Myocytes, Cardiac / drug effects* Myocytes, Cardiac / metabolism Myocytes, Cardiac / pathology Obesity / etiology Obesity / genetics* Obesity / metabolism Obesity / pathology Palmitic Acid / pharmacology* Protein Binding Rats Signal Transduction Toll-Like Receptor 4 / genetics* Toll-Like Receptor 4 / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 12 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC02388 |