This Phase I STTR proposal has been substantially revised in response to the Study Section review. The proposal was written in response to the NIH Director's newly released }roadmap} that encourages collaboration between corporate and academic institutions to develop alternative models for conducting research and the suggestion by Dr. Francis Collins, Director of the National Human Genome Research Institute, that }academic pursuit of [the] first step in drug development could be particularly valuable}. This STTR Phase I proposal combines the talents of Zen-Bio, Inc., the leading commercial supplier of human adipose tissue-derived cells for pharmaceutical research, with those of an NIH-funded Botanical Research Center at the Pennington Biomedical Research Center, an internationally recognized center for studies of diabetes and nutrition, and Rutgers University, an internationally recognized center for the development of botanical extracts. Our overarching hypothesis is that botanicals may effect one or more tissue types in the development of metabolic syndrome and extracts that limit the amount of fatty acid }release} in adipose tissue (lipolysis or TG accumulation) will reduce the amount of ectopic peripheral fat accumulation and cardiovascular risk (e.g. niacin). In the Phase I proposal, we hypothesize that high-throughput screening assays using human adipose cell models will: (1) Identify novel lead compounds from an existing botanical library and; (2) Complement existing assays in the fractionation of extracts from botanicals with known benefits for obese, diabetic, or hypertensive patients. As the commercial partner, Zen-Bio brings an existing portfolio of high-throughput human cell-based assays for lipogenesis, lipolysis, and adipogenic gene expression profiling. As the academic partner, the Botanical Center at PBRC in collaboration with Rutgers University provides its unique library of botanical extracts and chemical fractionation expertise. In addition, the Botanical Center has already subfractionated botanical extracts from plants with identified therapeutic effects for cardiovascular disease, diabetes, and obesity. All of these tools and reagents will be available for the proposed studies. Prior studies validate the utility and efficacy of this approach. The murine 3T3-L1 pre-adipocyte cell line has been used to screen a combinatorial chemical library for lead compounds promoting or inhibiting adipogenesis (2); however, it is well known that compounds identified in murine models often fail as human pharmacological agents. PUBLIC HEALTH RELEVANCE: The chemicals identified through this STTR may have potential application in the treatment of obesity, diabetes, and metabolic syndrome. The outcome of this work will have direct commercial implications for both Zen-Bio and the Pennington Biomedical Research Center in terms of potential products, licensing opportunities, and intellectual property. [unreadable] [unreadable] [unreadable]