Journal
EMBO MOLECULAR MEDICINE
Volume 7, Issue 11, Pages 1418-1425Publisher
WILEY-BLACKWELL
DOI: 10.15252/emmm.201505731
Keywords
cholesterol; lipid absorption; lymphatic vasculature; obesity; VEGF-C
Categories
Funding
- Leducq Transatlantic Network of Excellence in Lymph Vessels in Obesity and Cardiovascular Disease [11CVD03]
- Marie Curie ITN Vessel consortium of Seventh Framework Program of European Union [317250]
- Academy of Finland Centre of Excellence in Translational Cancer Biology [271845]
- European Research Council [ERC-2010-AdG-268804]
- Finnish Cancer Research Organizations
- Sigrid Juselius Foundation
- Biomedicum Helsinki Foundation
- Ida Montin Foundation
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Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. TheVegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism.
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