Original investigation

Cardiovascular Diabetology

, 11:72

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Gemma AragonèsAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
  • , Paula SaavedraAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
  • , Mercedes HerasAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
  • , Anna CabréAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
  • , Josefa GironaAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
  • , Lluís MasanaAffiliated withResearch Unit on Lipids and Atherosclerosis, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili Email author 

Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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

Keywords

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