The aim of this research is to better understand the brain pathways regulating appetite, to design better drugs that would decrease hunger and help treat obesity. We focus on brain pathways sensing protein, because proteins are really efficient at suppressing hunger. We are identifying and characterising specialized cells in the brain that can tell how much protein we’ve eaten and in response to that, make us feel hungrier or more sated.
Growing evidence indicates that human obesity is a disease of brain pathways regulating appetite. The characterization of these pathways to eventually develop safe and efficient therapies mitigating hyperphagia is one of the top priorities in obesity research. Although protein is known to be the most potent appetite suppressant among all macronutrients, little is known about how the mammalian brain senses protein availability to create neural representations that guide behaviour and modulate metabolism. The goal of this programme is to characterise the central representation of protein abundance and determine whether brain protein sensing pathways can be targeted to produce satiety and improve energy balance.
We hypothesise that the branched-chain amino acid leucine signals protein abundance to brain circuits controlling appetite and metabolism. During the past 5 years, we have characterised hypothalamic leucine-sensing neurons and are developing strategies to specifically target these neurons using molecular genetics. We are developing gain- and loss-of-function approaches to test the role of discrete leucine-sensing neuronal populations in the control of appetite and energy balance in mice. Using these models, we are testing the role of specific neuronal populations in leucine and protein sensing, in the regulation of energy balance and in the response to diets with varying protein contents. We are planning to characterise the neural circuits downstream from leucine-sensing neurons, and determine how these circuits are integrated with energy sensing neural circuits controlling appetite and weight.