Fetal programming of cardiometabolic disease

Obesity and related diseases such as insulin resistance and diabetes are prevalent worldwide. Diabetes in parents is a risk factor that makes cardiovascular and metabolic diseases more likely in offspring (embryonic programming). However, little is known about the underlying epigenetic mechanisms. The term epigenetics refers to the inheritance of properties that are not determined by genes. The research team wants to find out more about the epigenetic mechanisms of embryonic programming. The aim is to identify epigenetic targets that could prevent cardiovascular and metabolic diseases in the next generation through therapeutic intervention.

Coordination

Prof. Michael Bader
Max Delbrück Center for Molecular Medicine

Prof. Ralf Dechend
Prof. Michael Schupp

Charité - Universitätsmedizin Berlin

Team

Natalia Alenina
Max Delbrück Center for Molecular Medicine, Co-PI

Michaela Golic
ECRC, Clinician Scientist

Joachim Spranger
Charité - Universitätsmedizin Berlin, Co-PI

Till Schütte
Charité - Universitätsmedizin Berlin, PhD student

Three questions for the team

Ralf Dechend, Co-PI
Ralf Dechend, Co-PI

1. What is the new idea behind your project?

We are exploring the molecular mechanisms of embryonic programming – a novel approach that we hope will enable us to learn more about the causes of susceptibility to chronic diseases in adulthood. For our work, we have developed an animal model that we can use to produce temporally controlled insulin resistance during pregnancy by disabling the insulin receptor. This animal model is unique and allows us to identify diabetes-induced epigenetic regulators and relate these to the development of cardiovascular and metabolic diseases.

2. How does your project fit in with BIH’s international work?

We are continuing our work on the molecular level and working in cooperation with basic and clinical researchers to find new therapeutic approaches and help people with this condition. We are therefore planning to collect and process complete genome sequences in the BIH Core Facility Genomics and BIH Biobank. We need these data to be able to characterize the “epigenetic fingerprint” of parental diabetes in offspring.

3. How might patients benefit from your results one day?

We already know that parental diabetes is a risk factor for cardiovascular and metabolic diseases in offspring. Which molecular mechanisms are involved in transmitting the disease risk, however, is largely unknown. Our results will provide important insights into the (patho)physiological impact of parental disease, which may help in the development of new, targeted therapeutic approaches. For instance, this could lead to “epigenetic prevention” to reduce the likelihood of cardiovascular and metabolic disease developing in the next generation.