Metabolism Research Cores
A goal of the NUIP program is to increase engagement with scientists working in complementary but distinct disease areas, most of which have a metabolic component. To advance this NUIP initiative, we utilize and support university-sponsored technology platforms that allow for comprehensive metabolic assessments in clinical cohorts and disease models. These platforms are of broad utility to investigators across the institute and enable formation of collaborative research teams and sharing of resources.
Metabolic Phenotyping Core (Director – Anil Laxman)
Metabolic impairments (e.g. hyperglycemia, insulin resistance, dyslipidemia, etc.) associated with diabetes and heart disease elicit the formation of toxic nutritional metabolites implicated in disease pathogenesis. For example, imbalances in fuel storage vs. oxidation gives rise to reactive oxygen species, citric acid cycle intermediates, harmful lipid species, branched chain amino acids, and other metabolic by-products that disrupt tissue function. The University of Utah Metabolic Phenotyping Core avails researchers with capabilities for profiling mitochondrial function and metabolic homeostasis in tissue samples and model organisms.
- Techniques for Laboratory Animals: Indirect calorimetry, insulin sensitivity determinations (i.e. euglycemic clamps, GTT, ITT, etc.), blood chemistry (triglycerides, cholesterol, inflammatory markers, etc.), body composition analysis (MRI), blood flow, telemetry, vascular reactivity, and exercise capacity and tolerance.
- Techniques for Cells and Tissues: Tissue function determinations (islets, heart, muscle, aorta, and hepatocytes), Langendorff heart perfusions, vascular reactivity, etc), Oxygen consumption, mitochondrial complex activity and assembly, ROS production, ATP synthesis, mitochondrial membrane potential, TCA intermediates and activities, acyl-carnitines, mitochondrial imaging, mitochondrial fusion and fission
Metabolomics Core (Director – James Cox, support from the HSC)
Though the number of distinct metabolites in a particular tissue is low in comparison to those measured by other “omic” technologies, metabolomic profiling holds great promise for the elucidation of cellular mechanisms which underlie disease pathology and potential toxicological effects of drug therapies. In particular, metabolomics measures chemical phenotypes that are the net result of genomic, transcriptomic, and proteomic variability, thereby providing a remarkably integrated profile of biological status.
Not surprisingly, alterations in nutrient metabolism are fundamental features of diabetes, cardiovascular disease, cancer, infection, and neurobehavioral disorders. Thus, the application of metabolomic technologies could facilitate the identification of biomarkers and therapeutics for diseases which lie at the core of University of Utah Health. Targeted mass spectroscopy to quantify metabolites in the following classes: sphingolipids, glycerolipids, sterols, amino acids, acylcarnitines, and organic acids. Efforts are ongoing to expand fluxomic capabilities.