Over 50% of adults in the European Union (EU) countries are overweight and therefore at risk of developing metabolic diseases such as type 2 diabetes or non-alcoholic steatohepatitis. The characteristics of modern lifestyle, such as excessive consumption of food and sedentary behavior, contribute to this situation. But we also see changes in the rates of food intake and sleep / wake patterns that contribute to overweight and metabolic complications. Almost 20% of the working population in the EU countries work in shifts (3.5 million workers for France alone). However, the mechanisms linking irregular lifestyles to overweight and metabolic complications are poorly understood.

The rationale for our research program is based on the following observations:
1. The liver plays a central role in adapting to physiological alternation between fasting / fed state.
2. Liver metabolism is regulated by an internal clock.
3. The control of mitochondria by the hepatic clock is essential to the normal functioning of the liver (Jacobi et al., Cell Metabolism 2015).

We therefore use in vitro and in vivo approaches to study hepatocyte metabolism. Genetic, pharmacological, and metabolic approaches are used to delineate the molecular mechanisms by which overnutrition and loss of circadian synchrony disturbs mitochondrial rhythms. Then, we establish how these alterations trigger metabolic diseases.

The future of chronobiology research is translation to clinical medicine. Our project is a fundamental part of this endeavor, as it provides the preclinical proof of concept for moving scientific basis to clinical research on metabolic diseases.
We take advantage of the unique environment of l'institut du thorax and its research unit to demonstrate the relevance of our results in clinical populations of obese patients.



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