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Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-κB pathway

International Journal of Obesity volume 33, pages 465–472 (2009)Cite this article

Abstract

Background:

Visfatin is an adipokine that is highly expressed in visceral fat. Plasma levels of visfatin have been reported to be higher in subjects with obesity and/or type 2 diabetes mellitus. However, the role of visfatin in endothelial dysfunction has been largely unexplored.

Objectives:

We investigated the possible pathogenic role of visfatin in endothelial dysfunction, particularly focusing on its effect on inflammatory mediators.

Design:

Primary human umbilical vein endothelial cells (HUVECs) pretreated with visfatin (1, 10 and 50 ng ml−1) were used to study the relationship between visfatin and endothelium dysfunction. Expressions of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and cytokines (interleukin (IL)-6 and IL-8) affected by visfatin were investigated by enzyme-linked immunosorbent assay, flow cytometry and real-time PCR. Activity of nuclear factor (NF)-κB was examined by electrophoretic mobility shift assay.

Results:

At a visfatin concentration of 50 ng ml−1, significant increases in IL-6, IL-8, ICAM-1, VCAM-1 and E-selectin gene expression along with increased IL-6, IL-8 and sE-selectin protein levels in the conditioned medium were detected. Flow cytometry showed that the addition of visfatin significantly increased ICAM-1 expression and VCAM-1 expression (10 and 50 ng ml−1, respectively). Electrophoretic mobility shift assay confirmed that visfatin increased the DNA-binding activity of NF-κB. In addition, pretreatment with visfatin (10 and 50 ng ml−1) increased human monocyte cell line THP-1 adhesion to HUVECs.

Conclusions:

Our findings suggest that visfatin causes endothelial dysfunction by increasing inflammatory and adhesion molecule expression at least partly through the upregulation of NF-κB activity.

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Acknowledgements

This study was supported by grants from Taichung Veterans General Hospital (TCVGH-963001C; TCVGH-967308B; and TCVGH-OCIT968409), Taiwan, and the National Science Council (NSC 95-2314-B-075A-020-MY3), Taiwan, Republic of China.

Author information

Author notes

  1. W-J Lee and C-S Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC

    W-J Lee, C-S Wu & C-M Wu

  2. Social Work Department, Tunghai University, Taichung, Taiwan, ROC

    W-J Lee

  3. Department of Life Science, National Chung Hsing University, Taichung, Taiwan, ROC

    C-S Wu & H Lin

  4. Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC

    I-T Lee & W H-H Sheu

  5. Department of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC

    I-T Lee & W H-H Sheu

  6. Department of Obstetrics and Gynecology, National Chung-Hsing University, Taichung, Taiwan, ROC

    J-J Tseng & M-M Chou

  7. Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan, ROC

    W H-H Sheu

  8. College of Medicine, National Yang Ming University, School of Medicine, Taipei, Taiwan, ROC

    W H-H Sheu

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Correspondence to W H-H Sheu.

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Lee, WJ., Wu, CS., Lin, H. et al. Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-κB pathway. Int J Obes 33, 465–472 (2009). https://doi.org/10.1038/ijo.2009.24

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