The development of obesity. Insulin resistance, and metabolic syndrome Involves dysfunction of multiple organ systems and occurs In a complex and progressive fashion. In the initial funding cycle, small animal metabolic phenotyping was used to establish that two of the botanical extracts under study at our Center and (i.e. artemlsia dracunulus L., Incarnatin) ameliorated the developmental pathology ofthis process. More Importantly, this experimental strategy provided key insights regarding the tissue sites where beneficial effects were realized. The evolution of our experimental approach in the next cycle involves combining small animal metabolic phenotyping with the analytical power of metabolomic profiling to obtain the biochemical phenotypes that will provide insights Into the pathogenesis of Insulin resistance, and the mechanisms engaged by botanical extracts to ameliorate the progression. The Integrative Biology Core will combine state-of-the-art in vivo metabolic phenotyping with detailed ex vivo proteomic and metabolomic profiling of serum and tissue samples to provide highly Integrated metabolic signatures of the pathophysiology of insulin resistance and its resolution by botanical extracts. The Integrative Biology Core will be located at the Pennington and will be comprised of 2 interactive components: the Animal Research Subcore and the Analytical Chemistry Subcore, comprised of a Clinical Chemistry/Stable Isotope component and a Proteomic/Metabolomic component. The Integrative Biology Core will function Interactively with the Project leaders, the Administrative Core and the Botanical Core in all phases of experimental planning, execution, analysis, and interpretation. The overall goal of the IBC is to bring the combined expertise of all elements of the Botanical Research Center to bear upon our collective efforts to provide novel insights Into these mechanisms. We will use rodent models of obesity/diabetes to evaluate the mechanism of botanical extracts to ameliorate the development of this pathology, conducting detailed in vivo metabolic phenotyping to establish efficacy and guide timing of tissue harvest for rigorous ex vivo metabolomic profiling. The resulting biochemical signatures will be used to gain Insights Into the mechanism of action of botanical extracts.
The ability to obtain metabolic snapshots of substrate fluxes through metabolic pathways that integrate carbohydrate and lipid metabolism affords us an exciting opportunity to gain new molecular and physiologic insights Into the successful resolution of pathogenic mechanisms by our selected botanicals.
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