Obesity and its co-morbidities are major threats to the health of Americans. In less than 20 years, the prevalence of obesity increased from 30.5% to 42.4%, and the prevalence of severe obesity increased from 4.7% to 9.2%. The mission of the Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules (NPOD) is to prevent, treat and cure obesity and co-morbidities with bioactive food compounds. The focus on bioactive food compounds is a unique niche in obesity research and has afforded NPOD with tools to ameliorate obesity and co-morbidities through consumer-friendly, economically feasible adjustments to their diets with a negligible effect on taste. In Phases 1 and 2, NPOD has delivered on NIGMS expectations. NPOD has increased its member base 4.9-fold to 59 faculty in 26 departments (representing 571 trainees) at University of Nebraska- Lincoln (UNL; lead institution), University of Nebraska Medical Center (UNMC; strategic partner), and University of Nebraska Omaha. This growth was achieved through nine tenure-leading faculty appointments, recruiting faculty not previously engaged in obesity research, and providing a home for obesity researchers who previously worked in isolation. To date, NPOD members have secured nearly $195 million in external research funding, a nearly 36:1 return on institutional investment. UNL and UNMC have contributed nearly 3500 square feet and $5.5 million to NPOD in Phases 1 and 2 with additional institutional commitments in Phase 3 and the three years following. Most of the new space was leveraged to develop a new Research Core (Biomedical and Obesity Research Core, BORC), which provides state-of-the art services for research on obesity and bioactive food compounds unique in Nebraska. BORC has fulfilled 1400 service requests per year that generated $266,335 in annual revenue. NPOD is poised to continue its strong trajectory toward sustainability in Phase 3 and beyond through five pillars of NPOD sustainability: institutional commitments, F&A costs, philanthropy, program project grants, and NIDDK funding through the Nutrition and Obesity Research Center (NORC) mechanism. NPOD's pursuit of sustainability will be guided by the following Specific Aims. Specific Aim 1: Implement NPOD's succession plan to achieve sustainability through preparing former Research Project Leaders and a new hire to serve as future Center Director. Specific Aim 2: Lead BORC into long-term sustainability by attracting new users, particularly external users, through continued alignment of services offered with user needs and strengthened promotional activities. Specific Aim 3: Increase NPOD's critical mass of investigators conducting clinically important research through the Center's Pilot Grants Program and a new faculty hire in a tenure leading appointment and expertise in electronic health records. Specific Aim 4: Increase NPOD's revenue by prioritizing pilot grant applications with a high likelihood of leading to large-sc...