Illustration of intestinal villi absorbing fat molecules via lymphatic vessels, emphasizing VEGFR-3's role.

Gut Check: How Your Body's Fat Absorption System Could Be the Key to Better Health

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Beau Callahan in Health & Wellness August 2025 • 5 min read.

"New research uncovers the hidden role of VEGFR-3 signaling in regulating triglyceride retention and absorption in the intestine, potentially unlocking future treatments for metabolic disorders."


Imagine a sophisticated highway system inside your body, dedicated to transporting fats from the food you eat to where they're needed for energy and other essential functions. This system relies on tiny vessels in your intestines called lacteals, which absorb dietary fats packaged as chylomicrons. For years, scientists believed this was a passive process, but now they're discovering it's a highly regulated and dynamic operation.

At the heart of this regulation is a crucial molecule called Vascular Endothelial Growth Factor-C (VEGF-C). This major lymphangiogenic factor is known to maintain lacteal function, but the precise role of its partner, the tyrosine kinase VEGF receptor 3 (VEGFR-3), in fat absorption has remained a mystery. New research is shedding light on this critical interaction.

A recent study published in Frontiers in Physiology has uncovered how VEGFR-3 signaling plays a pivotal role in triglyceride (TG) absorption and distribution within the body. The research team used a unique mouse model, called Chy, with a specific mutation that inactivates VEGFR-3. The results revealed a surprising connection between VEGFR-3 signaling and how our bodies process dietary fats, offering new insights into potential therapeutic targets for metabolic disorders.

The VEGFR-3 Connection: How it Impacts Fat Processing

Illustration of intestinal villi absorbing fat molecules via lymphatic vessels, emphasizing VEGFR-3's role.

The study's findings revealed that when VEGFR-3 is not functioning correctly, it leads to a cascade of effects that disrupt the normal fat absorption process. Specifically, the researchers observed:

Researchers investigated the role of VEGFR-3 signaling in triglyceride (TG) absorption. They used a mouse model, Chy, with an inactivating mutation in the tyrosine kinase domain of VEGFR-3 (heterozygous A3157T mutation resulting in I1053F substitution). The research shows that inactivation of VEGFR-3 tyrosine kinase motif leads to disrupted TG processing.

  • Fat Retention: Triglycerides tend to accumulate within the cells lining the small intestine (enterocytes).
  • Reduced Plasma TG Levels: After a meal, the levels of triglycerides in the blood are lower than normal.
  • Increased Fecal Excretion: More free fatty acids (FFAs) and triglycerides are excreted in the stool.
  • Nitric Oxide Reduction: Levels of nitric oxide (NO), a molecule needed for chylomicron mobilization, are significantly reduced in the intestine after a fat-rich meal.
These findings support the idea that VEGFR-3 signaling is crucial for the efficient transfer of chylomicrons, which are the packages that transport triglycerides, from the enterocytes into the lacteals. If this process is impaired, it can affect how fats are distributed and used throughout the body. All of the impacts on the body could change how fats are distributed and used throughout the body. The findings suggest that VEGFR-3 has an important role in helping fats enter the lymph system in the gut, possibly impacting how they're moved around the body.

The Future of Fat Absorption Research: Targeting VEGFR-3

This research opens up new avenues for understanding and potentially treating metabolic disorders related to fat malabsorption. By identifying VEGFR-3 signaling as a key regulator in this process, scientists can now focus on developing targeted therapies to improve fat processing in the gut.

One potential strategy could involve finding ways to enhance VEGFR-3 signaling in individuals with impaired fat absorption. This might involve developing drugs or other interventions that stimulate VEGFR-3 activity or increase the production of nitric oxide, which is essential for chylomicron mobilization.

While more research is needed to fully understand the implications of these findings, this study provides a valuable foundation for future investigations into the role of VEGFR-3 in metabolic health. By unlocking the secrets of fat absorption in the gut, we may be able to develop new strategies to combat obesity, improve nutrient utilization, and promote overall well-being.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3389/fphys.2018.01783, Alternate LINK

Title: Vegfr-3 Signaling Regulates Triglyceride Retention And Absorption In The Intestine

Subject: Physiology (medical)

Journal: Frontiers in Physiology

Publisher: Frontiers Media SA

Authors: Trevor Shew, Nathan E. Wolins, Vincenza Cifarelli

Published: 2018-12-11

Everything You Need To Know

1

What is VEGF-C and what role does it play in fat absorption?

VEGF-C, or Vascular Endothelial Growth Factor-C, is a major lymphangiogenic factor known to maintain lacteal function, which is crucial for fat absorption in the intestines. While VEGF-C is known to be important, research is now focusing on its partner, VEGFR-3, to understand the specifics of how it impacts fat absorption.

2

How did the Chy mouse model contribute to understanding VEGFR-3's function in fat absorption?

The Chy mouse model, which has an inactivating mutation in the tyrosine kinase domain of VEGFR-3, was instrumental. By studying these mice, researchers could observe the effects of impaired VEGFR-3 signaling on triglyceride absorption, distribution, and related metabolic processes. This model allowed the researchers to determine that inactivation of the VEGFR-3 tyrosine kinase motif leads to disrupted TG processing.

3

What happens when VEGFR-3 signaling doesn't function correctly, according to the study?

The study found that when VEGFR-3 signaling is impaired, several things happen: triglycerides accumulate in the enterocytes (cells lining the small intestine), plasma triglyceride levels decrease after meals, fecal excretion of free fatty acids and triglycerides increases, and nitric oxide levels in the intestine are reduced. These changes suggest that VEGFR-3 is essential for the efficient transfer of chylomicrons from enterocytes into lacteals, impacting fat distribution and utilization.

4

What are the potential therapeutic implications of this research on VEGFR-3 signaling and fat absorption?

This research suggests that targeting VEGFR-3 signaling could lead to new treatments for metabolic disorders related to fat malabsorption. By understanding how VEGFR-3 regulates triglyceride processing, scientists can develop therapies to improve fat absorption in the gut. Further studies could explore specific drugs or interventions that enhance or restore VEGFR-3 function to normalize fat metabolism. This will improve the delivery of fat to be stored or used as energy, it can also help to prevent disease such as cardiovascular.

5

What are lacteals, and how do they relate to VEGFR-3 and fat absorption in the gut?

Lacteals are small vessels in the intestines responsible for absorbing dietary fats that are packaged as chylomicrons. They are a critical part of the fat absorption system, transporting fats from the intestines to other parts of the body. VEGF-C maintains lacteal function, while VEGFR-3 regulates how triglycerides are processed within this system. Lacteals ensure that our body gets fat soluble vitamins and dietary fats for proper health and body maintenance.

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