This proposal builds upon the accomplishments made during the previous funding cycle and requests continuing support of the Center of Biomedical Research Excellence (COBRE) on Obesity and Cardiovascular Diseases (COCVD). Kentucky ranks within the top 10 states for the prevalence of obesity and cardiovascular diseases, and the epidemic is not abating. Thus, it is imperative that mechanisms linking obesity to cardiovascular diseases are identified. During the 4 years of support the COCVD has made significant strides advancing knowledge on obesity-associated cardiovascular diseases through support of junior investigators and the development of research cores. As a result, we have experienced outstanding success, with graduation of 75% of 12 supported junior investigators to independent R01 support, including 15 new NIH R01s. The program has graduated 2 junior faculty/year to NIH R01 level support, with 125 publications from junior investigators, and an additional 318 publications from mentors. In addition, we have supported 7 pilot projects that have contributed to 58 publications. New research cores to quantify obesity phenotypes and to provide analytical services in lipidomics have markedly increased the research infrastructure. As a direct result of COCVD activities, the institution competed successfully for a CTSA to establish the Center for Clinical and Translational Sciences. In the second phase of the COCVD we propose to create a nationally recognized Center of Research Excellence to define mechanisms linking the epidemic of obesity to cardiovascular diseases, the primary cause of death in the obese population. To accomplish this goal, we will (1) develop a critical mass of funded investigators including basic and physician scientists with research programs directly related to the Center's unifying theme, (2) provide strong mentoring programs, (2) recruit new investigators to the Center through pilot project grant support, which will be leveraged by the institution and the CTSA, (4) expand and further develop an Analytical Core (with a focus on lipidomics), a Physiologic Core to quantify obesity and cardiovascular phenotypes, and a Pathology Core to assess tissue histology.