Neuro-hormonal control of hunger, nutrient tolerance and food intake : from nutrient sensing to reward sensitivity.

Intense signalling occurs between the gastrointestinal tract and the brain. Under normal conditions, most of these signals are not perceived. We will test the hypothesis that this “Gut-to-Brain” signalling is in fact crucial for the control of food intake. We propose that the capacity for the stomach to relax during food intake, as well as the activation of anti-nociceptive pathways during meal ingestion are crucial determinants of the volume of ingested meals. We also hypothesize that maximal motor activity of the gastrointestinal tract between meals (so-called gastric phase 3), controlled by clock genes and ghrelin / motilin release, triggers hunger peaks and thereby determines meal frequency. We will study whether synaptic transmission and specific enteric nerve circuits are influenced by orexigenic and anorexigenic messengers, to synchronize central and peripheral pathways involved in food intake. Under pathological conditions, normally unperceived Gut-to-Brain signalling may reach perception levels. This phenomenon, referred to as visceral hypersensitivity, causes unexplained symptoms and may also interfere with the normal control of food intake.