Gut epithelial control of nutrient reward

ABSTRACT/PROJECT SUMMARY The negative health burden of obesity leads to an estimated 500,000 deaths in the United States annually. Obesity and related metabolic disorders are caused by the excess consumption of palatable, densely caloric foods. People with obesity have diminished reward from food. Although the taste of food can elicit a rewarding feeling, the intestine is required for food reward. How the gut signals this reward to the brain is unknown. My long-term career goal is the document the physiologic regulation of food intake for better treatment of obesity. With the support of the NIH Mentored Research Scientist Development Award – K01, the objective of this proposal is to define the role of a specialized intestinal sensory cell in food reward and obesity. This proposal is built on recent fundamental discoveries that have established how nutrient choice is guided by specialized neuropod cells in the duodenum. Building on these observations, the objectives of this proposal are three-fold: (1) to establish the role of duodenal neuropod cells in reward-driven feeding; (2) map the functional brain targets of duodenal neuropod cells; and (3) determine the effects of duodenal neuropod cells on hyperphagia and obesity. Defining how reward is signaled from the gut to the brain to guide ingestive behavior will allow for novel pharmacotherapies for the treatment of obesity. Together with my mentoring team, we have designed this project to provide me with the necessary research and professional training for me to excel as an independent investigator at the intersection of gastroenterology and neuroscience.