Effect of visfatin on the function of endothelial progenitor cells in high-fat-fed obese rats and investigation of its mechanism of action

Abstract

The aim of this study was to study the quantity change of endothelial progenitor cells (EPCs) in obese rats fed a high-fat-diet and to investigate the correlation of EPC numbers with visfatin. The impact of visfatin on the quantity and function of EPCs were further investigated by cell culture methods. Male Wistar rats were fed on either a standard diet (NC group) or a high-fat diet (HF group) for 16 weeks. Serum visfatin, Lee's index and the protein expression of visfatin in viseral adipose tissue (VAT) were determined. Bone marrow EPCs in 2 groups of rats were isolated, cultured and counted. EPCs primarily cultured from control male Wistar rats were treated with different concentrations of visfatin. The quantity, migration and adhesion capacity of EPCs were evaluated after visfatin treatment. Protein expression of nuclear factor-κB (NF-κB) in the nuclei of EPCs was detected. After 16-week feeding, body weight, serum visfatin, Lee's index and visfatin contents in viseral fat were significantly increased in the HF group compared with NC group (P<0.01 or P<0.05). The quantity of EPCs primarily cultured from rats in HF group was lower than that in NC group. The quantity of EPCs was negatively correlated with serum visfatin levels, visceral fat, fasting blood glucose, HOMA-IR, total cholesterol, triglyceride and body weight (P<0.01). In cultured EPCs, visfatin significantly increased the protein expression of NF-κB in EPC nuclei (P<0.01) in a dose-dependent manner. The migration and adhesion capacity were impaired by visfatin treatment (P<0.01). In conclusion, bone marrow-derived EPCs decrease in number and have impaired migration and adhesion function in high-fat-fed obese rats, along with increased serum visfatin and protein contents in VAT. Visfatin may have an impact on the quantity and function of EPCs through the NF-κB pathway.

Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells

“…Also, visfatin adversely affects the migration and adhesion capacities of EPCs through activation of NF-jB [312]. These effects are consistent with visfatininduced ED in the setting of metabolic syndrome.…”

Visfatin induces the apoptosis of endothelial progenitor cells via the induction of pro-inflammatory mediators through the NF-κB pathway

“…Due to its role in inflammation, visfatin has been implicated in the pathogenesis of various metabolic disorders, such as metabolic syndrome, type 2 diabetes mellitus and obesity ( 6 , 7 , 27 ). Our previous studies also revealed that visfatin treatment impaired the migration and adhesion capacity of EPCs ( 19 ). A possible mechanism through which visfatin exerts these effects lies in the inflammation induced by visfatin, which may upregulate a series of inflammatory factors, leading to the apoptosis of EPCs and resulted in the reduction of their number and function ( 19 ).…”

“…Our previous studies also revealed that visfatin treatment impaired the migration and adhesion capacity of EPCs ( 19 ). A possible mechanism through which visfatin exerts these effects lies in the inflammation induced by visfatin, which may upregulate a series of inflammatory factors, leading to the apoptosis of EPCs and resulted in the reduction of their number and function ( 19 ). Inflammation in EPCs has also been linked to pro-inflammatory adhesion molecules, which can be inducers of leukocyte recruitment ( 28 ).…”

“…Emerging evidence has established a potential link between adipokines and vascular dysfunction, while our previous studies have correlated EPC dysfunction in obese rats with serum visfatin levels ( 19 ), with higher levels of serum visfatin and a lower level of circulating EPCs in the obese population ( 7 ). However, the specific mechanisms remain unclear, and few studies have specifically investigated visfatin and EPCs, and the related mechanisms of action.…”

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair

“…84 The number of blood EPCs was associated with blood NAMPT levels. Sun et al 85 showed that high-fat diet decreased the number and impaired the functions of bone marrow-derived EPCs, which were negatively correlated with serum NAMPT levels. Chen et al 86 demonstrated that obese men had higher levels of serum NAMPT and a lower level of circulating EPCs compared with controls.…”