Obesity and diabetes are complex disorders that have emerged as major health concerns worldwide. The complexity inherent in these disorders with respect both to their pathogenesis and metabolic consequences has heightened the need for interactive groups of investigators that unite multidisciplinary approaches with overlapping research interests. The goal of this proposal is to provide a group of five closely interacting investigators with a comprehensive, state-of-the-art resource for energy balance/metabolic phenotyping of rodent models relevant to nutrition, obesity, diabetes or related disorders. Each investigator is NIH-funded and employs mouse and/or rat models to investigate the pathogenesis of obesity, inflammatory anorexia, insulin resistance and metabolic dysfunction, and each has a well-defined requirement for improved metabolic analysis capability. Meeting this need will be accomplished through the purchase of the TSE LabMaster / PhenoMaster (TSE Systems, Midland, MI) apparatus, which offers numerous advantages over alternative systems for rodent metabolic phenotyping. This system provides a series of interrelated measures pertinent to rodent energy metabolism in up to 16 rats or mice simultaneously. Indirect calorimetry is used to monitor rates of oxygen consumption and carbon dioxide production by monitoring gas concentrations entering and exiting the chamber and computing the difference between them. This information in turn yields measures of the rates of oxygen consumption (VO2, a measure of energy expenditure), CO2 production (VCO2), heat production, and respiratory exchange ratio (RER, also known as respiratory quotient, which describes the relative oxidation of fat versus carbohydrate as a source of fuel by the animal). Combined with simultaneous measures of locomotor activity, wheel running activity, and body temperature (by telemetry), this system provides not only measures of total energy expenditure, but clarifies whether differences in energy expenditure are due to changes of body temperature, physical activity, metabolic rate, or some combination of these. Moreover, the optimal parameter for normalizing calorimetry data is lean body mass, and this will be determined for each animal using one of our two state-of-the-art magnetic resonance spectroscopy (MRS) units (one for rats, the other for mice) purchased from Echo Medical Systems and housed in space adjacent to where the TSE calorimetry apparatus will be located. Lastly, this system also offers real-time measures of food and liquid intake, allowing quantitative analysis of energy intake (including meal patterning), as well as energy expenditure. This system, therefore, provides comprehensive, quantitative information that is critical for metabolic phenotyping of rodent models of obesity and diabetes.
The prevalence of obesity has reached epidemic proportions in the US and other developed countries, and is causally linked to a dramatic, global increase in the prevalence of type 2 diabetes. Despite major technological advances, including the application of genetic, physiological and pharmacological tools in rodent models, the pathogenesis of these common metabolic disorders remains poorly understood, and treatment options are limited. The current proposal is intended to support quantitative metabolic phenotyping of rodent models of obesity and related disorders undertaken by a group of interactive, NIH-funded investigators who will soon relocate to a new research facility. Obtaining the requested equipment will critically advance the ability of this group to conduct their studies and will support synergistic interactions between investigators with distinct but overlapping interests.
