ABSTRACT The DRC Regional Metabolomics Core at Princeton provides Penn DRC investigators with access to state-of- the-art metabolomics and flux analysis. These capabilities allow DRC investigators to measure, both broadly and quantitatively, metabolic activity in cell culture, animal model, and clinical specimens relevant to diabetes and obesity. Now entering its 5th year, the Core has seen steadily increasing usage and is on track to analyze over 5000 samples in 2016. Thus, investigator demand for its services are high. This reflects the Core's position as a leader in metabolomics and lipidomics, with a particular focus on integration of these technologies with isotope tracing to reveal dynamic metabolic activity. In Aim 1, the Core will provide metabolomics services covering approximately 300 water-soluble metabolites and approximately 500 lipids. This will be achieved via mass spectroscopy-based analytical methods validated for their specificity and quantitative reproducibility. Aim 2 focuses on isotope tracer studies. To this end, the Core will guide tracer study design, carry out labeling pattern measurement, and facilitate data interpretation for both cell culture and in vivo research. Methods are now in place to trace major circulating nutrients in mice, and are being actively utilized to investigate mouse models of obesity and diabetes. Aim 3 involves expansion of the Core's capabilities. Beyond continuous improvement in breadth, depth, and quantitative reproducibility of metabolome coverage, this will include (i) new methods for in vivo tracing and (ii) establishment of a new joint Penn-Princeton Clinical Metabolomics Team to further increase clinical application of the Core's capabilities. The net effect will be to augment the scientific and clinical impact of the DRC through use of transformative metabolomics and flux analysis approaches to better understand?and thereby eventually more effectively diagnose and treat? diabetes, obesity, and related metabolic disorders.