University of Michigan Medical School to study the science of obesity and metabolism

As millions of Americans prepare their New Year’s resolutions to lose weight, eat better or exercise more, the University of Michigan Medical School is launching a new center that may help explain why so many resolutions fail, while others succeed.

The new University of Michigan Metabolomics and Obesity Center will explore the science behind weight gain and loss, through molecular-level research on how the body breaks down and uses food, and how metabolism varies among individuals.

It will bring together physicians and basic science researchers from across the U-M campus and provide scientific tools to help them carry out experiments. It will also help launch new research projects by granting seed funding, help train new scientists specializing in metabolic research, and enable scientific findings to be turned into practical information that can be used to help overweight and obese people.

Two-thirds of Americans, including an increasing number of children, are overweight or obese – setting the stage for obesity-related illnesses from diabetes and heart disease to stroke, cancer, and bone and joint problems.

“Obesity is a huge public health challenge, but also a major scientific challenge,” says center director and U-M metabolism researcher Charles Burant, M.D., Ph.D. “We still don’t understand why the same food intake can lead to weight gain in one person but not another, nor why diabetes develops in some overweight people but not others. We hope to accelerate progress in understanding weight gain, weight loss and metabolism at the most basic levels, and to help translate that understanding to clinical practice.”

Burant, whose own laboratory research focuses on how the body processes sugars and fats, is an Associate Professor in the Metabolism, Endocrinology and Diabetes division of the Department of Internal Medicine, and in the Department of Molecular & Integrative Physiology. He also has an appointment in the U-M Division of Kinesiology.

One of the new center’s priorities is to explore the metabolome: the collection of small molecules (metabolites) created by the breakdown of food to be used or stored by the body.

Like the genome, which contains all the body’s genes, and the proteome, the collection of all the proteins encoded by those genes, the metabolome can be catalogued and analyzed in a way that can yield scientifically useful information. The new center will allow scientists to measure metabolites in blood, tissue, cells and more, giving them the means to understand how those levels change in response to changing food and nutrient intake – and how that change varies from person to person.

Another key goal of the center is to foster research on the metabolic phenotypes of both humans and research animals. By making specific measurements of how individuals’ bodies use food or specific nutrients, researchers involved with the center will be able to tell how specific genes and underlying characteristics influence the tendency to gain weight.

Burant notes that a key part of this effort will be cooperation among researchers from many areas of the U-M, and the leveraging of existing U-M facilities.

For example, the center will involve Jeff Horowitz, Ph.D., of the U-M Division of Kinesiology, who studies human weight gain and metabolism using facilities such as the U-M Health System’s General Clinical Research Center.

And, together with the Michigan Diabetes Research and Training Center, headed by William Herman, M.D., MPH, the center will develop facilities where researchers can perform sophisticated measurements on animals that have been bred or genetically engineered as models of human metabolic characteristics.

One such test, which measures how sensitive the muscles and liver are to insulin in the blood, involves sugar that has been tagged with short-lived radioactivity, to allow it to be traced as it moves through the bloodstream and is taken up by tissue with the help of insulin. This kind of testing, when performed as part of larger studies on genes and proteins, can help researchers understand the variation between individuals and the resulting differences in weight gain and loss.

In addition to the two “core” efforts for human and animal phenotyping, and the metabolomics effort, the center will involve two other major areas of emphasis: systems biology and clinical research.

The systems biology effort will work with the National Center for Integrative Biomedical Informatics, based at the U-M, to harness computing power in a way that can bring together information on proteins, genes, metabolites and human or animal phenotypes related to metabolism and weight. This will help scientist make sense of the very large amounts of data gathered through different experiments by their teams and others.

The clinical research effort will involve physicians and others who treat both adults and children for obesity and related disorders. By bringing research scientists into contact with the clinical world, Burant says, ideas formed in the laboratory can be tested in humans – and researchers can find potential participants for their studies. Burant notes that the center is forming connections with U-M’s obesity, cardiovascular and bariatric surgery programs, as well as programs in the Department of Pediatrics for children and teens who are overweight or have special risk factors.

In all, Burant says, the new center will take a comprehensive approach to the basic research, clinical translation and education needed to carry obesity research forward. With more and more Americans failing on their weight-loss resolutions each year, the need has never been greater.

http://www.med.umich.edu/medschool

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