New Findings by UM Researchers Could Lead to Obesity Treatments

10/30/2007

New findings published by University of Miami Miller School of Medicine researchers suggest possible new targets for treating obesity. Using functional magnetic resonance (fMRI) imaging scientists were able to determine the brain circuits involved in hunger that are influenced by a hormone called leptin. The new research was published in the October 29 online edition of the Proceedings of the National Academy of Science.

In previous clinical trials, supplementation of leptin, the signaling molecule produced by fat cells, produced moderate weight loss in some obese patients, purportedly by inhibiting hunger and promoting feelings of being full.

"In this new study we used fMRI to measure brain activity before and after supplementation in three adults from a Turkish family who lacked the leptin hormone due to an extremely rare genetic mutation that prevented their bodies from producing any leptin at all," said Julio Licinio, M.D., professor and chairman of the Department of Psychiatry and Behavioral Sciences at the Miller School of Medicine and senior author of the study.

It was Licinio who learned of the family through a paper published in the journal Nature Genetics, which first described the mutation. Three of the family members, all cousins and all severely obese, were flown to UCLA (where Licinio worked at the time) for clinical research treatment with leptin.

"In a study published in 2005, we showed that within months they all lost a dramatic amount of weight, and they now continue to be followed by me every six months at the University of Miami Miller School of Medicine, having just traveled here just last month," said Licinio. "This family is the best model to study leptin because they dont have it, and there are probably less than 15 people in the world today with this genetic mutation. We have been studying the cousins continually since 2001, and we have been able to generate a very important body of work related to obesity, and our research will continue to move forward at the Miller School of Medicine."

During the current study, a team of collaborating researchers at UCLA, led by Edythe London, Ph.D. showed images of food to the three adults both before and after leptin treatment, while fMRI imaging was taking place. After leptin replacement in these individuals, feelings of hunger induced shown by activity in certain brain regions were reduced, while brain activity increased in the prefrontal cortex, an area of the brain previously associated with feeling full or satisfied.

"This research shows there are very specific brain activation patterns that are related to obesity," said Licinio. "The more we can learn about these patterns, we will be able to better understand the mechanisms by which people become obese."