Grant: Doctoral Research Award - PA: RPP - Newfoundland and Labrador

Obesity rates have sharply increased over the past few decades, thereby reducing the quality of life of Canadians. To develop efficient therapies for obesity, we need to understand the regulation of body weight at its source - the brain. The brain coordinates behaviour and physiology to adapt to changing feeding states, such as after a meal or during fasting. However, this balance between food intake and requirement can be overcome by an abundance of rewarding energy-dense food, leading to overeating and obesity. Within the hypothalamus, neurons expressing the neuropeptide orexin are of particular interest for obesity since they are linked to both appetite and reward circuitry and are known to promote consumption of rewarding energy-dense food. Therefore, the goal of my research is to discover how orexin neurons can promote obesity. Recently, research has shown that synaptic plasticity, a process by which appetite circuits change their properties or wiring, is critical for body weight regulation in the brain. Accordingly, my preliminary studies show that a rewarding, energy-dense diet induces plasticity that increases the excitatory drive to orexin neurons. This increased drive would further promote appetite leading these rats to overeat. Therefore, I hypothesize that there are changes to the orexin circuit induced by exposure to a rewarding energy-dense diet, which cause overeating and weight gain. To test this hypothesis, the electrical activity of orexin neurons will be recorded from rats fed with a normal or rewarding energy-dense diet. I will measure various properties of the circuits within the orexin network to assess how they change between feeding conditions.This study is important as dysfunction in this network could be a beginning or sustaining cause of overeating leading to obesity.