Central Control of Feeding Behaviour and Energy Expenditure

Circulating signals of hunger and satiety such as hormones (leptin, ghrelin) or nutrients are integrated at the level of the brain. The detection and integration of theses signals by dedicated neuronal substrate leads to adaptive metabolic and behavioral response which in turn will affect food intake and energy expenditure. Using genetic tools and integrated approaches our team is interested in the cellular and molecular basis of central control of feeding behavior, energy expenditure and nutrient partitioning and its implication in the etiology of obesity and diabetes.

The modern abundance of energy-rich foods combined with a shift to more sedentary lifestyles has led to a thermodynamic imbalance, and consequently, excessive caloric intake and reduced energy expenditure are the main causes for the prevalence of obesity. According to the World Health Organization (WHO), the worldwide obesity has more than doubled since 1980. In 2008, 1.5 billion adults, 20 and older, were overweight. Obesity is now also considered as an epidemic by the French Health system. A recent report from the French SENAT pinpoints the dramatic progression of obesity in France and a « Plan Obésité » has been launched in 2011 under the highest authorities. According to the WHO, the fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended. And it is a fact that globally, there has been both an increased intake of energy-dense foods that are high in fat, salt and a decrease in physical activity.

In adult mammals energy homeostasis is finely regulated. Blood glucose levels, body weight, and fat content remain within narrow ranges and experimentally-induced perturbations (e.g., food restriction) invariably result in a rapid return to ‘set point’ when normal conditions are restored. To accomplish this, circulating peripheral factors such as hormones (e.g., insulin, leptin, ghrelin) and nutrients (e.g., glucose, lipids) activate discrete neural circuits in the brain that trigger changes in the basal metabolic rate and/or feeding behaviour. Disruption of these neural circuits can give rise to life-threatening conditions that include metabolic diseases such as obesity and diabetes in both humans and rodent models. Therefore it is crucial to understand the mechanism that insures the proper equilibrium between energy intake and expenditure.

The core approach of the COFFEE team is to leverage the power of modern molecular genetic tools and mouse models in integrated approaches in order to dissect out the role of discrete neural circuit elements in the control of different aspect of energy balance including feeding behavior notably in its rewarding & motivational component together with energy expenditure and nutrient partitioning.

Team members

A new article from Cécile Haumaitre and collaborators discusses the origin of pancreatic lesions associated with pancreatic cancer

Diabetes Institute, From inflammation to cancer in digestive diseases, Publications

Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer death worldwide. It is projected to become the second leading cause of cancer death by 2030. Unfortunately, PDAC is often diagnosed at an advanced stage, resulting in a 5-year survival rate of less than 10%. Since the most common precancerous lesions of PDAC are currently not clinically detectable, understanding the mechanisms that lead to their formation and progression is crucial to enabling early diagnosis and more effective therapeutic intervention.