Scientists Win $2.4 Million to Develop New Strategies to Fight Obesity

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded $2.4 million from the National Institutes of Health (NIH) to identify the brain circuits involved in weight control and to develop novel strategies to fight obsessive eating and obesity.

Baoji Xu, a TSRI professor, is the principal investigator of the new four-year study.

“Our long-term goal is to understand the mechanisms that govern control of energy balance in our bodies,” Xu said. “When we finally understand the processes that regulate that balance, we can exploit those findings to develop novel interventions for obesity.”

Despite the enormous cost, there is currently no effective and safe treatment available for obesity, which raises the risk of everything from stroke to diabetes and cancer. Research published last year in JAMA Internal Medicine found that more than two-thirds of Americans are either overweight or obese, a major increase over the last 20 years.

For the new study, Xu and his colleagues will focus on a specific protein and its receptor that play a not-well-understood role in regulating the body’s energy balance. This protein is known as brain-derived neurotrophic factor (BDNF), and its receptor is TrkB.

“Although great progress has been made in understanding other energy-regulation molecules, no one realized the importance of the BDNF-TrkB pathway in controlling body weight until about 10 years ago,” Xu said. “Much less is known about this mechanism than many others.”

Xu’s own research has played a key role in demonstrating a clear role for BDNF in controlling body weight. Some preliminary studies in his laboratory found that the deletion of the TrkB gene in various sections of the brain in animal models resulted in moderate to severe obesity plus an abnormal rise in appetite and reduced physical activity.

“Since we moved to Scripps Florida, we have greatly increased our effort in dissecting the mechanism by which BDNF regulates appetite and body weight,” Xu said. “We’ve gotten some very good results in identifying the neural circuits that carry out the activities of BDNF in suppressing appetite and stimulating energy expenditure. This new award will allow our laboratory to continue this effort.”

For advancing this research, Xu and his colleagues will employ viral vectors to selectively ablate gene expression in neural circuits and designer receptors exclusively activated by designer drugs (DREADD) to selectively activate or inhibit neurons.

The number of the grant, which was awarded by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, is 1R01DK105954.

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