Dissecting the gut-brain dynamics underlying anorexia

Project: Research project

Project Details


Energy homeostasis is maintained in large part through rapid, gut-brain communication, and this is disrupted across a broad range of diseases. Specifically, malnutrition and anorexia significantly increase morbidity and worsen quality of life in patients with a variety of inflammatory conditions. It has been clear for decades that inflammatory cytokines suppress appetite and perturb metabolism. However, virtually nothing is known about how these molecules alter the dynamics of the gut-brain axis and its regulation of appetite. We have shown that nutrient infusion directly into the gastrointestinal (GI) tract and resultant release of satiating hormones rapidly inhibits a population of hunger-promoting neurons – AgRP neurons – in the arcuate nucleus of the hypothalamus(1, 2). Recently, we used neural recordings in the same mice over months to examine for the first time how diet-induced obesity alters these dynamics(3). Collectively, our work was the first to evaluate in vivo gut-brain communication and its disruption in a disease state. These experiments also established our expertise at longitudinal monitoring of neural activity during the development and resolution of pathophysiology. We are now applying these tools to dissect the mechanisms of inflammationmediated anorexia, and this project will determine how inflammatory bowel disease (IBD) – an autoimmune condition frequently associated with malnutrition – alters gut-brain dynamics.
Effective start/end date2/1/221/31/25


  • McKnight Endowment Fund for Neuroscience (Letter 1/25/2022)


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