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Updated: Jan 31, 2026

The Isolation of Flowing Mesenteric Lymph in Mice to Quantify In Vivo Kinetics of Dietary Lipid Absorption and Chylomicron Secretion
Published on: November 30, 2022
VEGFR-3 Signaling Regulates Triglyceride Retention and Absorption in the Intestine
Trevor Shew1, Nathan E Wolins1, Vincenza Cifarelli1
1Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, United States.
Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) signaling is crucial for dietary triglyceride absorption. Its inactivation impairs chylomicron entry into lacteals, reducing plasma triglycerides and increasing fecal fat excretion.
Area of Science:
- Gastroenterology
- Molecular Biology
- Vascular Biology
Background:
- The lymphatic system is vital for dietary lipid transport via chylomicrons.
- Chylomicron entry into intestinal lacteals is an active, regulated process.
- Vascular Endothelial Growth Factor (VEGF)-C and its receptor VEGFR-3 are key in lymphangiogenesis and lacteal function.
Purpose of the Study:
- To investigate the role of VEGFR-3 signaling in triglyceride absorption and tissue distribution.
- To elucidate the mechanism by which VEGFR-3 influences chylomicron transport.
Main Methods:
- Utilized the Chy mouse model with an inactivating mutation in VEGFR-3.
- Analyzed triglyceride levels in plasma and tissues post-fat absorption.
- Measured free fatty acid and triglyceride excretion in feces.
- Assessed nitric oxide (NO) levels in intestinal tissue.
Main Results:
- Inactivation of VEGFR-3 led to triglyceride retention in enterocytes.
- Postprandial plasma triglyceride levels were decreased in Chy mice.
- Increased excretion of free fatty acids and triglycerides was observed in stools.
- Reduced nitric oxide levels in the intestine after a fat bolus were noted.
Conclusions:
- VEGFR-3 signaling is essential for efficient triglyceride absorption and chylomicron mobilization.
- Impaired VEGFR-3 function disrupts chylomicron entry into lacteals and NO generation.
- VEGFR-3 plays a critical role in the lymphatic transport of dietary lipids.
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