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

Renhai Cao, Ebba Brakenhielm, Claes Wahlestedt, Johan Thyberg, Yihai Cao

Research output: Contribution to journalArticlepeer-review

358 Scopus citations


Most endocrine hormones are produced in tissues and organs with permeable microvessels 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 fenestrations and permeability, and we characterize its angiogenic property in the presence of other angiogenic factors. We provide evidence that leptininduced new blood vessels are fenestrated. Under physiological conditions, capillary fenestrations are found in the leptin-producing adipose tissue in lean mice. In contrast, no vascular fenestrations were detected in the adipose tissue of leptin-deficient ob/ob mice. Thus, leptin plays a critical role in the maintenance and regulation of vascular fenestrations in the adipose tissue. Leptin induces a rapid vascular permeability response when administrated intradermally. Further, leptin synergistically stimulates angiogenesis with fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF), the two most potent and commonly expressed angiogenic factors. These findings demonstrate that leptin has another new function - The increase of vascular permeability.

Original languageEnglish (US)
Pages (from-to)6390-6395
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - May 22 2001
Externally publishedYes


  • Leptin
  • Neovascularization
  • Obesity
  • Vascular fenestrations

ASJC Scopus subject areas

  • Genetics
  • General


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