Asprosin Exacerbates Endothelium Inflammation Induced by Hyperlipidemia Through Activating IKKβ-NF-κBp65 Pathway

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-alpha 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-alpha, 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 IKK beta-NF-kappa Bp65 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.

Automated summary

Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. This study investigated the effect of Asprosin (ASP) on endothelium inflammation induced by hyperlipidemia. The results showed that ASP may play a pro-inflammation role in obesity-associated endothelium dysfunction, and could be a potential target for the prevention and treatment of obesity-related cardiovascular diseases.