Scientists discovered that a protein called FUNDC1 in blood vessel cells plays a major role in how our bodies handle extra food and develop obesity and type 2 diabetes. When people eat too much fatty food, this protein becomes more active and triggers a chain reaction that makes blood vessels less healthy and metabolism worse. In mice, removing this protein protected them from gaining weight and developing diabetes problems. This research suggests that blood vessel health is directly connected to weight gain and diabetes, opening new possibilities for treatments that target these vessels instead of just focusing on weight loss alone.

The Quick Take

  • What they studied: How a specific protein in blood vessel cells affects weight gain, insulin resistance, and the development of type 2 diabetes when eating a high-fat diet
  • Who participated: Laboratory mice genetically modified to lack the FUNDC1 protein, human cells grown in dishes, and tissue samples from people with obesity and type 2 diabetes
  • Key finding: Mice without the FUNDC1 protein in their blood vessel cells stayed leaner, had better insulin sensitivity, and avoided metabolic problems even when eating a high-fat diet, while normal mice developed these problems
  • What it means for you: This suggests that blood vessel health may be a key target for preventing or treating obesity and type 2 diabetes, though human treatments based on this discovery are still years away from development

The Research Details

Researchers used multiple approaches to understand how FUNDC1 works. First, they created special mice where the FUNDC1 gene was removed only from blood vessel cells, then fed them a high-fat diet to see what happened. They compared these mice to normal mice eating the same diet. The team also studied human cells in laboratory dishes and examined blood vessel tissue from people with obesity and type 2 diabetes to confirm their findings applied to humans. This multi-layered approach—using animal models, human cells, and patient tissue—strengthens the reliability of the conclusions.

By studying blood vessel cells specifically, researchers can understand how the vascular system (blood vessels) communicates with the rest of the body to control metabolism and weight. This is important because previous research focused mainly on fat cells and the liver, but blood vessels may be equally important. Understanding this connection could lead to new treatment strategies that work through a different biological pathway than current diabetes and obesity medications.

This research was published in Nature Communications, a highly respected scientific journal. The study used rigorous methods including genetically modified animals, controlled diet experiments, and human tissue validation. The findings were consistent across multiple experimental models (mice, human cells, and patient samples), which increases confidence in the results. However, the study was conducted primarily in laboratory and animal settings, so results may not directly translate to humans without further testing.

What the Results Show

When mice ate a high-fat diet, the FUNDC1 protein in their blood vessel cells increased significantly. This increase appeared to trigger a harmful chain reaction: the protein moved another protein called SIRT3 from the cell nucleus to the mitochondria (the cell’s energy powerhouse), which then allowed a third protein called GATA2 to become more active. This led to increased production of a substance called endothelin-1, which damages blood vessel function and worsens metabolism. In contrast, mice without FUNDC1 in their blood vessel cells did not experience this chain reaction. These mice remained significantly leaner, maintained better insulin sensitivity (their bodies responded better to insulin), and showed improved overall metabolic health compared to normal mice eating the same high-fat diet. The protective effect was substantial—the FUNDC1-deficient mice avoided the typical weight gain and metabolic dysfunction that occurs with high-fat diets.

The researchers found that in people with obesity and type 2 diabetes, blood levels of endothelin-1 (the harmful substance produced through the FUNDC1 pathway) were elevated and correlated with how much FUNDC1 was present in their blood vessels. This suggests the same mechanism discovered in mice also operates in humans. The study also showed that removing FUNDC1 specifically from blood vessel cells was more effective than removing it from other cell types, indicating that blood vessel cells are the critical location for this protein’s harmful effects on metabolism.

Previous research established that blood vessel dysfunction occurs in obesity and diabetes, but the specific mechanisms were unclear. This study provides a detailed molecular explanation for how blood vessel cells contribute to metabolic disease. It builds on earlier work showing that mitochondrial proteins regulate metabolism, but uniquely identifies FUNDC1 as the key link between blood vessel health and whole-body metabolic control. This represents a shift in thinking from viewing obesity and diabetes as purely problems of fat storage to understanding them as diseases involving blood vessel dysfunction.

The study relied heavily on laboratory mice, which don’t perfectly replicate human biology. While human cells and tissue samples were included, no human clinical trials were conducted, so we cannot confirm these findings work the same way in living people. The research focused on high-fat diet-induced obesity; results may differ with other causes of weight gain. Additionally, the study examined one specific protein pathway; other mechanisms contributing to obesity and diabetes were not explored. Long-term effects and potential side effects of targeting FUNDC1 in humans remain unknown.

The Bottom Line

Based on this research, there are currently no direct recommendations for patients, as this is fundamental research not yet translated to human treatment. However, the findings suggest that maintaining blood vessel health through regular exercise, avoiding excessive high-fat foods, and managing stress may be beneficial, as these factors support healthy endothelial function. People with obesity or type 2 diabetes should continue following their doctor’s current treatment recommendations while this research progresses toward potential new therapies. Confidence level: This is preliminary research; human clinical trials would be needed before any new treatments could be recommended.

This research is most relevant to people with obesity, prediabetes, or type 2 diabetes, as well as those at high risk for developing these conditions. It may also interest people concerned about metabolic health and cardiovascular disease prevention. Healthcare providers and pharmaceutical researchers should pay attention as this could lead to new treatment approaches. People without metabolic concerns can benefit from understanding that blood vessel health is connected to overall metabolism, supporting the importance of cardiovascular exercise and healthy eating.

This is early-stage research. If this pathway becomes a drug target, it typically takes 10-15 years to develop and test new medications in humans. In the nearer term (3-5 years), researchers may conduct additional studies to confirm these findings and explore whether existing drugs could be repurposed to target this pathway. Realistic expectations: significant clinical applications are likely 5-10+ years away.

Want to Apply This Research?

  • Track weekly cardiovascular exercise minutes and daily high-fat food intake. Monitor resting heart rate as a proxy for blood vessel health—improvements in resting heart rate may indicate better endothelial function. Log these metrics weekly to identify patterns between diet, exercise, and cardiovascular markers.
  • Implement a gradual reduction in high-fat food consumption (the study used high-fat diets as the trigger) while increasing aerobic exercise to 150 minutes per week. Use the app to set reminders for daily walks or cardio sessions and to log meals, creating awareness of fat intake patterns. Set a goal to replace one high-fat meal per week with a heart-healthy alternative.
  • Establish a baseline of current metrics (weight, resting heart rate, exercise frequency, diet composition) and track changes monthly. Use the app’s trend analysis to visualize improvements in cardiovascular fitness and metabolic markers over 3-6 months. Share data with healthcare providers during regular check-ups to monitor progress toward metabolic health goals.

This research describes laboratory and animal studies that have not yet been tested in human clinical trials. The findings do not constitute medical advice and should not be used to diagnose, treat, or prevent any disease. People with obesity, prediabetes, or type 2 diabetes should continue following their healthcare provider’s current treatment recommendations. Do not make changes to your diet, exercise routine, or medications based on this research without consulting your doctor first. This article is for educational purposes only and is not a substitute for professional medical advice.