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Open Access Open Badges Original investigation

Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

Gemma Aragonès1, Paula Saavedra1, Mercedes Heras1, Anna Cabré1, Josefa Girona1 and Lluís Masana12*

Author Affiliations

1 Research Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain

2 Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, C. Sant Llorenç 21, Reus, 43201, Spain

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Cardiovascular Diabetology 2012, 11:72  doi:10.1186/1475-2840-11-72

Published: 18 June 2012



Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro.


In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt).


We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production.


These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.

Diabetes; Endothelium; Fatty acid-binding protein 4 (FABP4); Endothelial dysfunction; Insulin; Insulin-signalling pathway; Endothelial nitric oxide synthase (eNOS); Nitric oxide (NO)