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Can dietary nitrate supplementation modulate xanthine oxidoreductase activity as a driver of metabolic syndrome complications in high fructose diets?

Code: BC-DTP_2026_12

Title: Can dietary nitrate supplementation modulate xanthine oxidoreductase activity as a driver of metabolic syndrome complications in high fructose diets?

Primary Supervisor: Cristina Perez-Ternero

Email: c.perez-ternero@qmul.ac.uk 

Institute: William Harvey Research Institute

Secondary Supervisor: Amrita Ahluwalia

Email: a.ahluwalia@qmul.ac.uk 

Institute: William Harvey Research Institute

 

Lay Summary:

 

What is metabolic syndrome? 

Metabolic syndrome is a group of health problems that often occur together. People with it may have extra weight around their waist, high blood sugar, high blood pressure, and unhealthy cholesterol. It is becoming more common and putting pressure on healthcare systems. 

How diet can cause problems 

Eating too much fat and sugar, especially a type called fructose, can cause metabolic syndrome and increase a substance in the body called uric acid, which can make these problems worse.  

A key enzyme 

An enzyme in the body called xanthine oxidoreductase (XOR) helps make uric acid and other harmful molecules that damage cells. But XOR can also make a helpful molecule called nitric oxide (NO), which is made from a substance called inorganic nitrate that is found in vegetables. NO keeps blood vessels healthy and supports bodily functions.  

Our research idea 

We want to see if we can help XOR make more of the good NO and less of the harmful uric acid by using dietary nitrate. The student will analyse XOR in human blood from people who have eaten high amounts of fructose and in mice fed a high-fructose, high-fat diet to see if nitrate, by making NO in the body, can reduce weight gain, improve blood sugar, and lower inflammation. 

Why this matters 

If this works, it could lead to a safe, inexpensive dietary approach to prevent metabolic syndrome. This could help people stay healthier and reduce healthcare costs, especially in communities with economic constraints. 

Aims:

The specific aims are to: 

  1. Characterise NO species concentration and XOR activity following fructose load in human plasma.
  2. Identify the tissue-specific source of XOR that contributes to UA elevation and MetS complications in response to HFHF diet.
  3. Determine whether modulating XOR activity through dietary nitrate supplementation, at a dose that achieves therapeutic nitrite levels in plasma, attenuates the metabolic effects of HFHF feeding in mice.

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