Open Access Research article

Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

Francisco José Tinahones123, Leticia Coín-Aragüez12, Maria Dolores Mayas12, Eduardo Garcia-Fuentes12, Carmen Hurtado-del-Pozo4, Joan Vendrell5, Fernando Cardona13, Rosa-Maria Calvo4, Maria-Jesus Obregon4 and Rajaa El Bekay12*

Author Affiliations

1 CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain

2 Laboratorio de Investigación Biomédica, Hospital Clínico Universitario Virgen de la Victoria, Campus de Teatinos s/n, 29010 Málaga, Spain

3 Servicio de Endocrinología, Hospital Virgen de la Victoria, Malaga, Spain

4 Instituto de Investigaciones Biomedicas (IIBM, CSIC-UAM]), Madrid, Spain

5 CIBERDEM. University Hospital of Tarragona Joan XXIII. IISPV, Rovira i Virgili University, Tarragona, Spain

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BMC Physiology 2012, 12:4  doi:10.1186/1472-6793-12-4

Published: 2 April 2012



The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR).


Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR.

Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM.


We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology.

Vascular Endothelial Growth Factor and Metalloproteinase; Obesity; Insulin Resistance; Omentum Adipose Tissue; Subcutaneous Adipose Tissue