Project Details
Projekt
HyperImaGene. Metabolic mechanisms that cause fat loss due to semaglutide versus muscle hypertrophy
Applicants
Nathalia Dragano, Ph.D.; Professor Dr. Martin Hrabe de Angelis; Professor Dr. Franz Schilling
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Out of a world population of ca. 8.1 billion women and men, 2.5 billion people are overweight and 890 million are obese. This is a major health problem as increased body weight is a risk factor for metabolic and other diseases. Stimulating global skeletal muscle hypertrophy commonly causes fat loss. In contrast, recently approved weight loss drugs such as semaglutide (marketed as Wegovy (R)) cause not only fat loss but also muscle atrophy. However, it remains to be studied how muscle hypertrophy alters the muscle metabolism, how the muscles' metabolite exchange with the circulation, how inter-organ metabolism is controlled especially between muscle and white adipose tissue and whether these changes of metabolism explain the metabolic health effects of skeletal muscle hypertrophy. The main aim of this project is to compare the metabolic mechanisms that explain the fat loss that results from global muscle hypertrophy with those responsible for the fat loss induced by semaglutide. We will study these two modes of fat loss and combinatorial treatments in mice models with genetic inhibition of Myostatin. For our studies we will employ advanced methods of metabolic research including arteriovenous metabolomics and metabolic flux analysis with stable isotope tracers. A unique focus of our project will be on metabolic imaging as this allows repeated non-invasive spatial quantification of metabolic mechanisms. Specifically, we will use longitudinal metabolic and fat magnetic resonance imaging (MRI) including hyper-polarized metabolites, and [18F]FDG-PET. Our research project is not only of scientific interest but is clinically important because it will help to inform treatment choices for billions of people with overweight and obesity worldwide.
DFG Programme
Research Units
