Dissecting sugar-induced modulation of gut-brain circuits

Excessive refined carbohydrate intake, particularly in the form of sugar-sweetened beverages, is a key driver of the diabetes and obesity epidemics. However, little is known about how high-sugar diets affect the neural circuits that regulate body weight and glucose homeostasis. My lab’s overarching goal is to understand how the nutritional regulation of gut-brain communication contributes to the development obesity and diabetes. We have previously shown that a high-fat diet dramatically and persistently dampens the activity of the gut-brain circuits that control appetite. We have now developed a sucrose over-consumption paradigm that we propose to combine with calcium imaging to understand how high-sugar diets alter nutrient-mediated gut-brain dynamics. Further, we will determine whether the behavioral and metabolic consequences of carbohydrate excess can be reversed by manipulating genetically defined neural populations along this axis. These studies will reveal in unprecedented detail how diets high in carbohydrate contribute to diabetes and obesity via altered neural circuit function, and will inform the development of novel circuit-targeted therapies for these metabolic disorders.