Astrocyte Aryl Hydrocarbon Receptor Signaling Is Necessary and Sufficient for Mediating Metabolic Homeostasis of Gut Microbiota-Derived Tryptophan Metabolites
Abstract
Obesity and diabetes rates continue to rise in both the general U.S. population and specifically in Veterans, underscoring a critical need to develop novel therapeutics to treat these metabolic diseases. Recent work has highlighted the importance of the gut bacteria in host metabolism, but the exact mechanism remains elusive. In the current proposal, we aim to determine the impact of tryptophan metabolites derived from ingested nutrient breakdown via the gut bacteria. We hypothesize that changes in these metabolites contribute to the development of obesity and diabetes via direct action in the brain on specific sites that regulate energy and glucose homeostasis. This proposal is highly innovative as it will demonstrate a direct link between the diet and gut microbiome with central nervous system function. This could lead to development of probiotics and specific dietary formulas to treat obesity and diabetes. This project is a great fit for several Peer Reviewed Medical Research Program Topic Areas. For example, this work corresponds with the Nutrition and Metabolism Portfolio Category, specifically in the Diabetes and Nutrient Optimization Topic Areas. Indeed, it fits multiple Strategic Goals: as a foundational study that aims to Understand correlations between nutrition and disease susceptibility, and as a Prevention study to Develop evidence-based diet and exercise recommendations to decrease obesity, improve nutrition, and optimize energy balance to prevent metabolic diseases. Indeed, this proposal will understand how diet-induced changes in tryptophan metabolism can impact metabolic disease and how treatment with these metabolites can prevent or ameliorate the development of obesity and diabetes. Furthermore, it aims to understand how the gut microbiome can impact specific areas in the brain that regulate metabolism, an extremely novel hypothesis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310058
Entities
People
- Frank Duca
Organizations
- United States Army
- University of Arizona