Metabolism can severely affect a healthy heart

Personalised Medicine and Health

Jeanine Prompers

In order to live, our body needs energy, which it extracts from food, mainly in the form of carbohydrates and fats. The cells in our body convert these fuels into energy, through chemical reactions, better known as metabolism. An imbalance or excess of food substances can lead to metabolic disorders, which increase the risk of developing type 2 diabetes and heart disease.

It’s common knowledge that people with diabetes have a much higher chance of developing heart disease which, unfortunately, is the most common cause of death in these patients. And it should be no surprise to learn that our hearts use an enormous amount of energy.

Lack of energy or inefficient use of energy lead to heart failure

The hearts of patients with heart failure (but no diabetes) display a shift in fuel balance towards sugar metabolism. Interestingly, the hearts of type 2 diabetes patients show a shift towards fats. Yet, both circumstances result in a similar phenotype of impaired heart function.

We want to understand how this occurs. It’s known that the failing non-diabetic heart cannot generate enough energy to work properly. The diabetic heart, on the other hand, has lots of energy in the form of fats, but cannot use this energy efficiently, leaving it energy-starved. Both cases lead to cardiac remodeling, which may include permanent structural (size and shape) and functional changes of the heart.

MRS to map relationships between energy use and heart failure

We’re using magnetic resonance spectroscopy (MRS) to non-invasively look at energy metabolism. In particular, we’re interested in the relationships between metabolic, structural and functional changes that take place during heart failure development in diabetic and non-diabetic hearts and aim to create a complete picture of remodeling in response to stress and injury.  

MRS (also called nuclear magnetic resonance, NMR) is a technique that is based on the same principles as magnetic resonance imaging (MRI). It uses a powerful magnet, radio waves and magnetic field gradients to non-invasively measure metabolites (intermediate molecules or products of metabolism) in different parts of the body.

Most of the clinical MRS studies are performed in the brain, but we are developing techniques to study metabolism in the heart

Because MRS and MRI use the same scanner, MRS is often combined with MRI to image changes in anatomy and function. Most of the clinical MRS studies are performed in the brain, but we are developing techniques for the 7 Tesla MRI scanner at the UMCU to study metabolism in the heart. This ultra-high field MRI scanner is powerful enough to allow us to see subtle changes in cardiac metabolism, morphology and function. This will aid the development of more effective therapies for different forms of heart failure, including regenerative medicine approaches, which in turn can be monitored using the same MRS and MRI techniques.

MR imaging and spectroscopy ecosystem

In Utrecht, we have a unique infrastructure for MR imaging and spectroscopy and have the strength of combining clinical research with studies in animal models and even smaller model systems such as organoids. We have critical mass to engage with: a huge, diverse group of researchers, clinicians, engineers and technical support. We have ultra-high field MRI machines: a 7 Tesla whole-body clinical MRI, one of about only 50 in the world; a 7 Tesla and 9.4 Tesla MRI for imaging in animal models; and a 22.3 T MRI for very small things. And we are active in method development for a variety of different applications. In fact, we are working on the development a new scanner specifically for imaging metabolism.

I draw energy from advancing both science and technology in parallel, and have experienced industry (PhD at Unilever), spending time abroad (post-doc in the USA), and a more technical environment (group leader at TU/e). Utrecht has all of these aspects and more, and offers a great environment for exploring the unknown.

Jeanine Prompers, PhD
Associate Professor
Biomedical MRI and MRS
UMC Utrecht