Grant: Operating Grant

Problems with the control of food intake are thought to contribute to the growing obesity epidemic in Canada and worldwide. The brain monitors and regulates how we acquire, store, and use energy from food. The brain gets signals from nerves that connect the brain to the intestines. Information also comes from substances in the bloodstream, made by organs such as the pancreas, the liver, and especially fat tissue. The hypothalamus, a small and ancient part of the brain, controls both food intake and energy output depending on these signals. We discovered a gene, called Magel2, which is most active in the hypothalamus. We made mice that are missing Magel2. These mice are less active and have more fat and less muscle compared to mice that have a normal Magel2 gene. The Magel2 protein is not made in people with a genetic disorder called Prader-Willi Syndrome (PWS). People with PWS continue to eat even when their stomachs are full, and they usually become very obese. In this project, we will find out why the hypothalamus in the mice without Magel2 does not properly respond to energy cues. By researching how Magel2 works in the brain to prevent excessive appetite and weight gain, we will further understand how the brain normally controls short-term food intake and long term body weight.