Angiogenesis Associated With Visceral and Subcutaneous Adipose Tissue in Severe Human Obesity

Author:

Ledoux Séverine12,Queguiner Isabelle1,Msika Simon2,Calderari Sophie1,Rufat Pierre3,Gasc Jean-Marie1,Corvol Pierre1,Larger Etienne14

Affiliation:

1. Institut National de la Santé et de la Recherche Médicale U833, Chaire de Médecine Expérimentale, Collège de France, Paris, France

2. Centre de l’obésité, Hôpital Louis Mourier, Assistance Publique–Hopitaux de Paris (AP-HP), Faculté de Médecine Xavier Bichat, Université Paris 7, Paris, France

3. Unité MSI-Département de Biostatistique, santé publique, et information médicale, Groupe Hospitalier Pitié-Salpetrière, AP-HP, Paris, France

4. Universite Rene Descartes, Paris, France

Abstract

OBJECTIVE—The expansion of adipose tissue is linked to the development of its vasculature. However, the regulation of adipose tissue angiogenesis in humans has not been extensively studied. Our aim was to compare the angiogenesis associated with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from the same obese patients in an in vivo model. RESEARCH DESIGN AND METHODS—Adipose tissue samples from visceral (VAT) and subcutaneous (SAT) sites, obtained from 36 obese patients (mean BMI 46.5 kg/m2) during bariatric surgery, were layered on chick chorioallantoïc membrane (CAM). RESULTS—Both SAT and VAT expressed angiogenic factors without significant difference for vascular endothelial growth factor (VEGF) expression. Adipose tissue layered on CAM stimulated angiogenesis. Angiogenic stimulation was macroscopically detectable, with engulfment of the samples, in 39% and was evidenced by angiography in 59% of the samples. A connection between CAM and adipose tissue vessels was evidenced by immunohistochemistry, with recruitment of both avian and human endothelial cells. The angiogenic potency of adipose tissue was not related to its localization (with an angiogenic stimulation in 60% of SAT samples and 61% of VAT samples) or to adipocyte size or inflammatory infiltrate assessed in adipose samples before the graft on CAM. Stimulation of angiogenesis by adipose tissue was nearly abolished by bevacizumab, which specifically targets human VEGF. CONCLUSIONS—We have established a model to study the regulation of angiogenesis by human adipose tissue. This model highlighted the role of VEGF in angiogenesis in both SAT and VAT.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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