Analysis of brown adipocyte-derived VEGF-A
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OBJECTIVE: While it has long been known that vascular endothelial growth factor A (VEGF-A) plays a role in vascular homeostasis, only recently have its effects been explored in adipose tissue. As perivascular adipose tissue (PVAT) is in close proximity with the aorta and coronary arteries and is known to contribute to vasodilation, it may influence vascular function via secretion of VEGF-A. The objective of this study is to analyze the effects of brown-adipocyte deletion of VEGF-A on circulating VEGF-A levels and distribution of VEGF-A isoforms. We hypothesize that ablation of VEGF-A in brown adipocytes will affect perivascular adipocyte and vascular function. MATERIALS/ METHODS: Mice harboring a brown adipose-specific VEGF deficiency, UCP1cre.VEGFflox/flox mice, were maintained on a chow diet. Primary adipocytes were isolated from brown adipose tissue (BAT) and thoracic PVAT by collagenase digestion and culturing. Gene expression was measured by RT-PCR from RNA extracted from tissues of UCP1cre.VEGFflox/flox mice. Circulating and tissue VEGF-A levels were quantified by ELISA. RESULTS: While VEGF-A ablation using the UCP1 promoter decreases VEGF- protein A levels in BAT and PVAT, it does not affect VEGF-A levels in the circulation. CONCLUSION: This study confirms the functional utility of the UCP1cre.VEGFflox/flox mouse model, as it selectively reduces VEGF-A levels in BAT and PVAT without affecting other tissues or circulating levels. As previous studies using VEGF ablation in all adipose tissues demonstrate an impaired thermogenic response and brown-adipocyte dysfunction, further study of the brown adipose-specific mouse model is warranted. Because PVAT provides protection against vascular stiffness, modulation of VEGF-A in PVAT may be a viable treatment for obesity-associated vascular complications.