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Lipidomic signatures of obesity and type 2 diabetes in humans: connection to circadian rhythm perturbations

Ursula Loizides-Mangold, University of Geneva
Hjelt grant holder 2019  
Ursula Loizides-Mangold 
University of Geneva
The worldwide increase in obesity and type 2 diabetes represents one of today’s biggest health challenges. Moreover, disruption of our body clock due to rotational shift work, jet lag and aging has additional negative effects on metabolism and contributes to the development of obesity and type 2 diabetes. In this project we will analyze the contribution of lipid (fat) metabolism to the development of obesity and diabetes and investigate, which role the biological clock plays in this context.

Fat molecules (lipids) are part of cell membranes, which are thin layers of lipids that form the boundary of living cells and internal cell compartments. Alternatively, lipids are also stored inside the cell in form of lipid droplets. This storage capacity is in particular important for adipose (fat) cells where lipid droplets serve as the main long-term energy store. Overall, there are thousands of distinct lipids in our body cells and lipidomics studies all of them and their relationships. In this project we will analyze the lipid composition of human skeletal muscle, adipose tissue and blood from lean, obese and type 2 diabetic human individuals and will search for differences between patient groups. Furthermore, we will analyze the effect of the biological clock on lipids found in human adipose tissue. We have recently discovered that levels of various types of lipids that are present in our muscle cell membranes vary during the day and could demonstrate that our biological clock is controlling these rhythms. In this project we will now investigate whether these lipid molecules are also rhythmic in human adipose cells and whether these oscillations are controlled by the body clock. Moreover, we will analyze if adipose cells produce signaling proteins (adipokines) in a rhythmic manner and whether their secretion is disturbed if the biological clock is not functional. Taken together, the findings of this study will allow us to identify, which lipid pathways are affected by obesity and type 2 diabetes and will hopefully lead to novel therapeutic approaches for diabetic patients. Moreover, the results of this project will also prepare the way for the identification of new biological markers for type 2 diabetes.
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