Discoveries made in the laboratories of Sanford-Burnham will, for the first time, advance to the clinical research stage involving human studies at the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes (TRI). The research will focus on orexin, an appetite-inducing hormone produced in the brain, which appears to resolve obesity without requiring a reduction in food consumption or elevation in physical activity. This research exemplifies the translational research focus at Sanford-Burnham and the TRI – advancing science from laboratory bench to patient bedside. The studies will provide insight into individual responses and contribute to the development of personalized therapies for treating metabolic diseases – a focus area for both the TRI and Sanford-Burnham.

Appetite-suppressing drugs have traditionally been the basis of weight-loss treatments since obesity is thought to be caused by excessive energy intake and low physical activity. However, appetite suppressants can produce unacceptable side effects and, after the treatment ends, patients usually the weight they lost. Recent data indicate that orexin leads to weight loss by releasing excess energy as heat instead of storing it.

“At the center of our study,” said Devanjan Sikder, D.V.M., Ph.D., assistant professor in Sanford-Burnham’s Diabetes and Obesity Research Center, “is an anti-obesity strategy that does not rely on reducing food intake. Instead, we focus on the energy expenditure and feeding-inducing properties of orexin.” He added, “My team has discovered that orexin activates calorie-burning brown fat, which we consider to be ‘good’ fat, and evidence strongly suggests that human obesity can arise from brown fat dysfunction.”

Brown fat burns high quantities of sugar and fat, a process that is designed by nature to moderate body temperature in babies, who have large numbers of brown fat cells. By finding a way to activate brown fat in adults, calories, which otherwise would be stored as unwanted white fat, can be burned. Orexin deficiency is associated with obesity in both animals and humans, while high orexin levels correlate with leanness.

“Advancing this orexin research to the TRI is a crucial first step in translating fundamental research at Sanford-Burnham to the clinical phase,” said Steven Smith, M.D., director of the TRI. “At the TRI we will conduct proof-of-concept experiments to validate this new drug target and test it for safety and efficacy.”

So far, orexin has only been tested in mouse models, where it has been shown to reduce fat by 50 percent, even under conditions of caloric excess. The fat loss is due to an elevation in the metabolic rate. During the study at the TRI, scientists will conduct clinical testing to assess orexin’s mode of action, efficacy and how it works in the human body, as well as evaluate the hormone’s acute effect in stimulating energy expenditure.

When it opens in March 2012, the TRI’s new 54,000 sq. ft. facility in Orlando, Florida, will contain a research clinic, imaging technology, a biorepository for sample collection and storage, as well as several other resources for metabolic studies. But the facility’s highlight will be the calorimeter rooms – small dormitory-style rooms that will allow TRI staff to measure fat and carbohydrate oxidation and energy expenditure as a person goes about his or her normal life. To make the best use of the generated data, the TRI is also building a superior informatics platform to collect and analyze their own research data, as well as personal and sample information for thousands of Florida Hospital patients. This database will help TRI, Florida Hospital and Sanford-Burnham scientists to better correlate patient information with data collected through laboratory research in Sanford-Burnham’s metabolomics laboratory.