Nesfatin-1 inhibits free fatty acid (FFA)-induced endothelial inflammation via Gfi1/NF-κB signaling.

Qingtao Meng, Qin Lu, Zhipeng Zhang, Jiyi Liu, Yu Lou, Yuwei Wang, Jihong Liu

Bioscience, biotechnology, and biochemistry 2021 Dec 22

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Nesfatin-1 is a neuropeptide produced in the hypothalamus. It is known that Nesfatin-1 is involved in food uptake, fat storage, and other metabolic regulation. We hypothesized that Nesfatin-1 may play a role in cardiovascular tissue. Free fatty acids (FFAs) are known to be the risk factor for cardiovascular diseases. FFA-mediated endothelial dysfunction is the critical mechanism of many cardiovascular disorders. The present study explores the protective effects of Nesfatin-1 on FFA-induced endothelial inflammation and the underlying mechanism. We found that significantly increased lactate dehydrogenase release and production of inflammatory factors were observed in FFA-treated human aortic endothelial cells (HAECs), accompanied by the enhanced attachment of U937 monocytes to HAECs and upregulated cell adhesion molecule vascular cell adhesion molecule-1, which were dramatically reversed by the treatment with Nesfatin-1. In addition, the promoted level of nuclear regulator NF-κB p65 and transcriptional function of NF-κB in FFA-treated HAECs were greatly suppressed by HAECs. Growth Factor Independent 1 Transcriptional Repressor 1 (Gfi1), an important negative regulator of NF-κB activity, was significantly downregulated in HAECs by FFAs and was upregulated by Nesfatin-1. Lastly, the inhibitory effects of Nesfatin-1 against FFA-induced NF-κB activation and adhesion of U937 monocytes to HAECs were abolished by the knockdown of Gfi1. In conclusion, our data reveal that Nesfatin-1 inhibited FFA-induced endothelial inflammation mediated by the Gfi1/NF-κB signaling pathway. © The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.

Citation

Qingtao Meng, Qin Lu, Zhipeng Zhang, Jiyi Liu, Yu Lou, Yuwei Wang, Jihong Liu. Nesfatin-1 inhibits free fatty acid (FFA)-induced endothelial inflammation via Gfi1/NF-κB signaling. Bioscience, biotechnology, and biochemistry. 2021 Dec 22;86(1):47-55