PROJECT SUMMARY/ABSTRACT This project supports the career development of Dr. Katherene Anguah in her path to become an independent translational researcher focusing on how dietary components may benefit cardiometabolic health through the control of appetite. The mentored plan builds on previous training by providing additional technical, academic, and professional development skills to facilitate research independence. An interdisciplinary team of mentors includes experts in human clinical feeding studies, functional magnetic resonance imaging, microbiome analysis, and stable isotope labeled, targeted metabolomics. The 5-year plan includes the opportunity to advance through both didactic instruction and experiences aimed at expanding skills in research management and scientific writing. Rationale: Strong evidence supports the association between high fiber (HiFi) diets (e.g. legumes, nuts, vegetables) and a reduced risk for chronic conditions such as cardiovascular disease (CVD), type 2 diabetes and some forms of cancer. However, the current U.S. average consumption of dietary fiber of 17g/day is significantly below the recommendation level of 25g/d for women and 38g/d for men. Furthermore, fiber fermentation to produce short chain fatty acid (SCFA) products and alterations in microbial composition and activity may be mechanisms linking a HiFi diet to improved health. Importantly, much of the data, including findings supporting a beneficial role of SCFA have been derived from animal studies. Human studies are now needed to advance the understanding of the translational significance of rodent studies and the potential benefit of fiber on microbial metabolites and cardiometabolic health, glucose regulation, appetite and satiety. The central hypothesis is that that the mechanisms by which dietary fiber provides metabolic benefit include direct physical effects in the upper gastrointestinal tract to slow nutrient absorption, and indirect effects to reduce food intake mediated by SCFA-induced secretion of intestinal hormones resulting in increased satiety. Design: Using fiber derived from peas, Aim 1 will test the effect of a HiFi diet on appetite, satiety, and cardiometabolic health and whether elevated SCFA concentration mediates improved satiety. Aim 2 will quantitate the changes in microbial composition and colonic SCFA production rate during HiFi feeding and whether any changes are potential mediators of observed benefits on satiety and cardiometabolic risk factors. Relevance: These studies will significantly expand the understanding of mechanisms by which dietary fiber improves satiety and cardiometabolic health in humans.