Angiogenesis towards Adipogenesis: Role of vascular endothelial growth factor

Atif, Amin Baig (2014) Angiogenesis towards Adipogenesis: Role of vascular endothelial growth factor. British Journal of Sports Medicine, 1 (1). pp. 1-2. ISSN 0306-3674

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Abstract

We are working with adipocytes and adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue (Corvera et al., 2013). Previous studies indicated that adipogenesis may be regulated by factors that drive angiogenesis. Fundamental aspects of angiogenesis, including basement membrane breakdown, vasculogenesis, angiogenic remodeling, vessel stabilization, and vascular permeability. Critical angiogenic factors include vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins (Ang), ephrins, matrix metalloproteinases, and the plasminogen enzymatic system. Vascular endothelial growth factor is the most critical factor because it initiates the formation of immature vessels and disruption of a single VEGF allele leads to embryonic lethality in mice. Expression of VEGF is influenced by hypoxia, insulin, growth factors, and several cytokines (Hausman et al., 2004). The VEGF has been reported to be modulated by leptin and hCG (Islami et al., 2003) and more recently the expression of angiogenic regulators, VGEF and leptin has been reported to be regulated by the EGF/PI3K/STAT3 pathway (Cascio et al., 2009). These vital findings reflects a regulation of secondary diseases related to obesity to be the result of complex molecular events and adipose tissue vasculature as a source of new targets for metabolic disease therapies. This gene is located on chromosome 11q13 (7 exons). VEGFB has been reported to have a role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation must be transported through the vascular endothelium to be metabolized by tissue cells. Bioinformatic analysis showed that VEGFB was tightly coexpressed with nuclear-encoded mitochondrial genes across a large variety of physiologic conditions in mice, pointing to a role for VEGFB in metabolism. VEGF specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb-/- mice showed less uptake and accumulation of lipids in muscle, heart, and brown adipose tissue, and instead shunted lipids to white adipose tissue. The co-expression of VEGFB and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated (Hagberg et al., 2012). In our study, we are also looking in to identify the mutation(s) in the VEGF-B gene in Malayisan Obese attributes towards CHD risk. We hypothesized, if there is a mutation in VGEF-B, then the obese subject will be predicted to have hypertension and if there will be no mutation then signs of metabolic syndrome and diabetes type II will be predicted in obese attribute in future. Most important the role of VEGF as major autocrine mediator of FGF-2-induced angiogenesis and proliferation (Naim et al 2005) should be considered by respective researchers in future.

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