UF researchers receive NIH grant to further explore gene therapy to decrease obesity

The National Institutes of Health has awarded University of Florida College of Medicine researchers a $1.8 million grant to continue exploring the use of gene therapy to treat obesity in animal models, as well as to assess its ability to postpone or prevent the onset of type 2 diabetes, an obesity-related illness.

In previous studies, UF scientists successfully used gene therapy to control appetite and weight in animal models for a short period.

Now researchers will investigate whether weight loss can be sustained for two to three years, and if the target weight can be maintained with a single injection or if a series of shots are required, said the study’s principal investigator, Satya Kalra, Ph.D., a neuroscientist in the Evelyn F. and William L. McKnight Brain Institute of UF.

The five-year study also will assess whether gene therapy can prevent obesity in rodents of normal weight. Rodents, like people, tend to put on weight as they age, which heightens the risk for obesity-related diseases.

Researchers will use the adeno-associated virus, an apparently harmless virus that exists in most adults, to deliver copies of the gene that produces the hormone leptin into the animals’ brains. Normally, fat cells naturally produce leptin and deliver it to the brain, where it helps control appetite and increases energy expenditure.

Previous UF studies have shown that leptin gene therapy also increases energy expenditure, which helps maintain weight. Results from both normal and obese rats and mice genetically altered to be overweight and fed either a high-fat or normal diet will be evaluated.

In addition, UF researchers will specifically look at leptin gene therapy’s effect on the onset of type 2 diabetes, which occurs when the body produces large amounts of insulin, but the cells fail to use insulin properly. Typically diagnosed in adulthood, type 2 diabetes is the most common form of the disease, and according to the American Diabetes Association about 90 percent of all people with newly diagnosed type 2 diabetes are overweight.

“If fat disposition contributes to the development of type 2 diabetes, and if our study shows that leptin gene therapy reduces fat and low weight is sustained, we expect that 100 percent of these animals will not develop type 2 diabetes,” said Kalra, who will work with co-principal investigator Pushpa Kalra, Ph.D., a professor of physiology.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, nearly a quarter of all adult Americans are obese, and each year approximately 280,000 adult deaths in the United States are attributable to obesity. Obesity is a major risk factor for heart disease, diabetes, stroke and hypertension.