Abstract—
Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. Vascular endothelium inflammation often occurs in patients with obesity. Asprosin (ASP) derived from white adipose tissue plays important roles in maintaining glucose homeostasis. However, effect of ASP on the vascular endothelium inflammation induced by hyperlipidemia and its underlying mechanism remains largely unclear. In this study, models of vascular endothelium inflammation were established to investigate the effect of ASP on the endothelium inflammation both in vivo and in vitro. Our data in vivo showed that recombinant ASP or high-fat diet (HFD) significantly increased the circulating levels of IL-6 and TNF-α and enhanced the adhesion of macrophages to endothelia characterized by the expression increase of CD68, ICAM-1, and VCAM-1 in rats. However, neutralization of ASP with an ASP specific antibody (AASP) significantly antagonized the changes induced by HFD. Similarly, our data in vitro also showed that ASP treatment elevated the expressions of IL-6, TNF-α, and ICAM-1 as well as VCAM-1. More important, our data revealed that the pro-inflammation effect of ASP was achieved by activating the IKKβ-NF-κBp65 pathway other than the oxidative stress pathway both in vivo and in vitro. In conclusion, our results demonstrate that ASP is a pro-inflammation player in the obesity-associated endothelium dysfunction. The findings would provide a novel target for the prevention and treatment of obesity-related cardiovascular diseases.
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Acknowledgements
We would like to appreciate the support from the National Natural Scientific Foundation of China (NSFC).
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This study was supported by the grants from the National Natural Scientific Foundation of China (81960153, 82260726).
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Qianqian Huang: formal analysis, writing–original draft, investigation, data curation. Sheng Chen: investigation, validation; Xiaowei Xiong: investigation, formal analysis; Yanan Zhang and Tingting Yin: formal analysis. Qiren Huang and Guohua Zeng: conceptualization, writing–review and editing, supervision, funding acquisition. All the authors have read and approved the manuscript.
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All animal procedures were approved by the Institutional Animal Care and Use Committee of Nanchang University School of Medicine and conducted in accordance with the guide for the Care and Use of Laboratory Animals published by the US National Institute of Health (NIH Publication No.85–23, revised 1996). For human ethics, not applicable.
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Huang, Q., Chen, S., Xiong, X. et al. Asprosin Exacerbates Endothelium Inflammation Induced by Hyperlipidemia Through Activating IKKβ-NF-κBp65 Pathway. Inflammation 46, 623–638 (2023). https://doi.org/10.1007/s10753-022-01761-7
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DOI: https://doi.org/10.1007/s10753-022-01761-7