Core Connection: Comprehensive Metabolic Phenotyping Core
October 4, 2018
| by Katie Neith
In order to understand the mechanisms of human diseases and how they might be treated, researchers often test theories and therapeutics in mouse models first. As both genetics and environmental stimuli can have an effect on the progression of illnesses and on the efficacy of treatments, one particularly important area of study in these animal models is metabolism, which lies at the intersection of many diseases.
At City of Hope, the Comprehensive Metabolic Phenotyping (CMP) Core provides sophisticated metabolic testing in mouse models of obesity, diabetes and cancer. Established in 2016, the CMP Core’s customers fit into one of three groups, says Patrick Fueger, Ph.D.
, the core’s founding director and associate professor in the Department of Molecular and Cellular Endocrinology: those needing assays using specialized equipment that is centralized in the core; those needing assays using specialized expertise that is unavailable in their own laboratory; and those wanting to use a centralized service core to free up their team’s availability and resources to conduct other experiments in their research program.
“Our services range from low to moderate throughput, from routine to incredibly sophisticated experiments, and from the use of minimal equipment to specialized equipment not usually contained in an individual research lab,” says Fueger. “A key aspect to the core is that we become partners in our customers’ research programs. We provide expertise on deciding what services to conduct, and help interpret the data and guide the study further, thereby elevating metabolic research on campus. In addition, we respond to our customers’ demands by continuously refining our procedures and will add services in response to the needs of our research community.”
The CMP Core is comprised of state-of-the-art equipment and expert staff who use standardized techniques for measurement that cut out confounding factors, ensuring that normal processes in the body do not skew results. The CMP team has the ability to perform a cadre of metabolic tests for investigators, including an assay for in vivo beta cell function that cannot be found anywhere else on the West Coast.
Equipment in the CMP Core includes, but is not limited to, a magnetic resonance imaging (MRI) unit for body composition analysis; an instrumented metabolic caging system for assessing food and water consumption, locomotor activity and energy expenditure; a rodent treadmill for forced exercise studies; running wheels in the metabolic caging system for voluntary exercise studies; and a work station to isolate tissues and hepatocytes (liver cells).
Fueger points to two services offered by the CMP Core that make it exceptional. First, the team recently acquired a new piece of equipment called the Promethion metabolic caging system that doubles their capacity to perform comprehensive studies in mouse models of diabetes, obesity and cancer. The platform allows them to measure both behavioral and physiological parameters central to energy expenditure and the regulation of body weight by housing mice individually in instrumented cages with a series of sensors and systems. This permits the measurements of food and water consumption, activity, body weigh, and gas exchange, which is used to calculate energy usage. Adaptation to cold and the effects of circadian rhythms can also be examined in the system. Together, these data are used to determine why an animal model might gain too much weight and develop type 2 diabetes or why a certain cancer might cause a mouse to rapidly lose weight.
And for investigators wanting to understand how their specific mouse model has altered glucose homeostasis, the CMP Core staff utilize clamp experiments, which were adapted and refined by Fueger to use in mice and have become the gold standards of metabolic research. For these experiments, catheters are surgically implanted into blood vessels, which enable researchers to access the circulation for both blood sampling and infusions in conscious, freely moving mice.
“We can then either measure pancreatic beta cell function by assessing insulin secretion in a living animal or insulin action in insulin-responsive tissues such as the liver, muscles and fat,” says Fueger. “Importantly, these studies are conducted with minimal stress to the animal, which is essential for impactful metabolic research.”
Collectively, the array of studies performed by the CMP Core allow research collaborators to pinpoint defects in metabolism at the organ level, which provide insights into the mechanisms of disease.
“We generate preclinical data for investigators that can be used for both target validation and mechanistic studies,” says Fueger. “Currently, we serve a mix between cancer and diabetes researchers at City of Hope, and in the future, we hope to extend our services to external customers in both academia and industry.”