Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF

Most endocrine hormones are produced in tissues and organs with permeable m icrovessels that may provide an excess of hormones to be transported by the blood circulation to the distal target organ. Here, we investigate whether leptin, an endocrine hormone, induces the formation of vascular fenestrati ons and permeability, and we characterize its angiogenic property in the pr esence of other angiogenic factors. We provide evidence that leptin-induced new blood vessels are fenestrated. Under physiological conditions, capilla ry fenestrations are found in the leptin-producing adipose tissue in lean m ice. In contrast, no vascular fenestrations were detected in the adipose ti ssue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tis sue. Leptin induces a rapid vascular permeability response when administrat ed intradermally. Further, leptin synergistically stimulates angiogenesis w ith fibroblast growth factor (FCF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. The se findings demonstrate that leptin has another new function-the increase o f vascular permeability.