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Bariatric surgery’s metabolic impact to be explored

Dec. 19, 2013, 9:49 AM

Vanderbilt University researchers have received a two-year, $1.2 million grant from the National Institutes of Health (NIH) to study a mouse model of the metabolic and hormonal changes caused by bariatric surgery.

Bariatric surgery is currently the only known effective treatment for severe obesity and type 2 diabetes in humans.

Understanding the cellular, molecular and genetic bases for the metabolic changes that result could potentially lead to improved pharmaceutical treatments and surgical techniques, said Roger Cone, Ph.D., the study’s principal investigator and chair of the Department of Molecular Physiology and Biophysics.

“The reason it’s important to work in the mouse,” Cone said, “is that it allows us to use state-of-the-art genetic technologies to understand the mechanism of bariatric surgery.”

Approximately 200,000 bariatric surgeries are performed each year in the United States. There are several different procedures, but all effectively reduce the size of the stomach.

Recent work has shown that in addition to the reduction in stomach size, there are likely many metabolic and hormonal changes underlying the beneficial effects of bariatric surgery. Currently, these changes are poorly understood.

Following bariatric surgery, 60 to 80 percent of patients with type 2 diabetes, for example, experience a complete resolution of the disease. Remarkably, this often occurs prior to any significant weight loss and may not be explained by the decrease in food intake alone.

Using surgical techniques pioneered by Dengpeng Yin, M.D., Ph.D., assistant professor in the Division of Hepatobiliary Surgery & Liver Transplantation, the researchers plan to use the mouse model to understand cellular signaling in both the brain and gut, and to determine how this signaling is affected by bariatric surgery.

In addition, they will attempt to determine why bariatric surgery fails to produce significant weight loss in a small number of patients. The BioVU DNA Databank will be used to identify genes that are associated with this failure.

“The … grant allows us to bring together novel and diverse expertise in central control of feeding, GI function and clinical bariatric surgery,” said David Wasserman, Ph.D., Annie Mary Lyle Professor in the Department of Molecular Physiology and Biophysics, and director of the Mouse Metabolic Phenotyping Center (MMPC).

Other co-investigators are Naji Abumrad, M.D., Kelli Boyd, Ph.D., DVM, Aurelio Galli, Ph.D., James Goldenring, M.D., Ph.D., Bingshan Li, M.D., Ph.D., and Owen McGuinness, Ph.D., from Vanderbilt, and Tamas Horvath, DVM, Ph.D., from Yale University.

The mouse bariatric research program was initiated with support from a 2009 Recovery Act supplement to the MMPC NIH grant, DK059637.

The study is supported by NIH grant DK096527. Other foundational work that led to the grant was made possible by the NIH-supported Vanderbilt Digestive Disease Research Center and Vanderbilt Diabetes Research and Training Center and by generous support from Vanderbilt University.

— by Emily Mason

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