Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF
Open accessAbstract
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 leptin-induced 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.
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Adipose tissue secretes several adipokines and endogenous angiogenesis inhibitors that modulate new blood vessel formation, including adiponectin, leptin, resistin, visfatin/thrombospondin 1, and plasminogen activator inhibitor.
“In addition to authentic angiogenic factors, AT secretes several important adipokines and endogenous angiogenesis inhibitors to modulate the balance of new blood vessel formation, including adiponectin (36,37), leptin (34), resistin (38), visfatin/thrombospondin 1 (39), and plasminogen activator inhibitor (40).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [34]
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- Authors
- Cao, R., Brakenhielm, E., Wahlestedt, C., Thyberg, J., & Cao, Y.
- Affiliations
- Karolinska Institutet (SE)
- Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Center for Genomic Research, Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-05-08
- Volume
- 98
- Issue
- 11
- Pages
- 6390-6395
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC33478
- OpenAlex
- W2111796479
- Cited by
- 446
- References
- 29
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 22 · 2021: 17 · 2020: 19 · 2019: 19 · 2018: 14 · 2017: 23 · 2016: 17 · 2015: 17 · 2014: 18 · 2013: 40 · 2012: 24
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, vascular permeability, angiogenesis, FGF2, vascular endothelial growth factor, adipose tissue, ob/ob mice, hormone transport
- MeSH terms
- Adipose Tissue, Animals, Capillaries, Capillary Permeability, Cattle, Cell Division, Cells, Cultured, Cornea, Drug Synergism, Endothelium, Vascular, Female, Humans, Lymphokines, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Obese, Fibroblast Growth Factor 2, Endothelial Growth Factors, Corneal Neovascularization, Neovascularization, Physiologic, Leptin, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice
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