Ebook Effects of weight loss after bariatric surgery for morbid obesity on vascular endothelial growth factor-A, adipocytokines and insulin.
Growth of any tissue requires the formation of a functional and mature vasculature. Adipose tissue, unlikeother organs, grows and develops continuously throughout life. In vitro studies showed that differentiating adipocytes and adipose tissue explants trigger blood vessel formation and that in turn adipose tissue endothelial cells promote preadipocyte differentiation. Furthermore, adipose tissue growth in mice can be impaired with angiogenesis inhibitors or inactivation of proangiogenic factors.
Vascular endothelial growth factor-A (VEGF-A) plays a pivotal role in both physiological and pathological angiogenesis through the increase of proliferation and migration of endothelial cells and permeabilization of blood vessels by inducing fenestrations in the endothelium. VEGF-A is highly expressed in adipose tissue and its expression increases significantly during adipocyte differentiation in several experimental models. This close relationship between adipogenesis and VEGF-A induced angiogenesis has been demonstrated in in vitro and in in vivo studies. The inhibition of angiogenesis by VEGF receptor-2 blocking antibodies not only reduced angiogenesis but also inhibited murine adipose cell differentiation.
Adipocyte-derived factors may play critical roles in regulation of tissue function by control of angiogenesis. Adiponectin is a circulating adipocyte derived cytokine with anti-atherogenic, anti-inflammatory, and anti-diabetic properties, which is decreased in obese individuals, while active angiogenesis occur in the adipose tissue. However, the interaction between adiponectin and angiogenesis has not been clarified. Some studies showed that adiponectin can stimulate new blood vessel formation in ischemic tissue and stimulate the differentiation of human endothelial cells into capillary like structures in vitro and blood vessel growth in vivo in a rabbit corneal assay. In contrast to these findings, it has been reported that adiponectin inhibits tumour neovascularization through its ability to induce endothelial apoptosis. Leptin has also been found to regulate angiogenesis. Leptin, another adipocyte-derived cytokine that plays a role in the control of satiety and energy expenditure, has been shown to promote angiogenesis in several in vitro and in vivo studies. Furthermore, leptin may potentiate VEGF-A mediated angiogenesis because leptin increased endothelial cell VEGF-A expression and secretion in a dose-dependent manner and acted synergistically with VEGF-A-driven angiogenesis in cornea pockets assays.
Some other hormones could have a role in the relationship between adipogenesis and angiogenesis. Ghrelin, a hormone isolated from the stomach, releases growth hormone and stimulates appetite. Ghrelin and its receptors are expressed in endothelial cells, but their function in blood vessels remains controversial. Some studies have demonstrated an antiangiogenic effect of ghrelin in human and rat in vitro assays and in vivo animal models. In contrast, a very recent study found that ghrelin significantly increased proliferation and migration of human microvascular endothelial cells in vitro. Finally, insulin has shown to activate hypoxia inducible factor-1 (HIF-1), the most potent stimulus for VEGF-A synthesis and secretion.
Modulation of development of the vascular network in adipose tissue may constitute a strategy to affect obesity. Therefore, it is important to obtain information on expression and functional roles of pro- and antiangiogenic components. However most of the data come from in vitro studies or animal models. Very little is known about the relationship between adipogenesis and angiogenesis in humans.
The aim of this study was to investigate the relationship between body mass index and serum concentrations of VEGF-A in obese human subjects and its modification after weight loss with bariatric surgery. We also analysed the association of circulating VEGF-A levels with other adipocytokines and hormones as adiponectin, leptin, ghrelin, and insulin in morbidly obese patients before and after weight loss with bariatric surgery. We selected patients who underwent different surgical techniques to search for differences in the analysed hormone levels due to different anatomic alterations.
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