PROJECT SUMMARY The long term goal of this project is to investigate the potential health benefits derived from dietary supplementation with black walnut extract using a rat model of obesity, diabetes, cardiovascular and liver disease. The project builds on previous studies that have shown that black walnuts have a diverse phytochemical profile that includes a number of compounds known to have advantageous, protective properties, e.g., antioxidant and anti-inflammatory effects in vitro. The specific objective of this proposal is to measure the impact of daily dietary supplementation with black walnut extract on relevant health parameters in the Zucker rat, a model of obesity and diabetes. In addition, a metabolomic approach will be undertaken to identify specific biomarkers related to hepatoprotective mechanisms conferred by walnut extract supplementation. The results of this study will identify specific, health-related benefits of black walnut extract supplementation, elucidate the modes of action, and allow our group to establish an efficient pipeline for evaluating plant-derived supplements and nutraceuticals. This pipeline will span from initial extraction, high- throughput screening, metabolomic profiling and biochemical analysis to characterization using in vitro assays and culminating in robust testing in rats with a variety of common human disease symptoms.