PET study links obesity to serotonin receptor

By using positron emission tomography to study the brain’s neuroreceptors in relation to obesity, scientists may be getting closer to determining important information about the neurobiological mechanisms involved, according to a group of Danish researchers. The study suggests the possibility of curbing appetite with future drugs. The findings were presented at SNM’s 53rd Annual Meeting this week in San Diego.

“From our molecular imaging research, we have discovered that overweight people have more of a certain type of serotonin receptor (the so-called 5-HT2A receptor) in their brains,” said David Erritzoe, research fellow with the Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging in Copenhagen, Denmark. Serotonin is a chemical compound in the brain involved in the regulation of many functions, including appetite, sleep and emotions, he added. “This relationship suggests that the 5-HT2A receptor is crucially involved in regulation of body weight and that the receptor should be exploited as a target for regulation of appetite,” said Erritzoe, co-author of “Overweight Associated With Increased Serotonin 2A Receptor Binding in Humans,” the first study to examine links between the 5-HT2A receptor and body weight.

Reports indicate that about 30 percent—or 60 million—of U.S. adults 20 years of age and older are obese, and the percentages of obese young people and children have risen considerably as well.

“This is the first study where a large number of healthy individuals have been studied to determine the association between 5-HT2A and body weight,” said Erritzoe. “We found that a high body mass index is associated with a high density of the 5-HT2A receptor in several brain regions—suggesting that overweight people have an upregulation (increase) of their brain 5-HT2A receptors,” he explained. “A number of drugs that block the 5-HT2A receptor are associated with weight gain; at the same time, studies in animals suggest that stimulation of the 5-HT2A receptor induces weight loss,” he noted. “Together, these findings point at a central role for the 5-HT2A receptor in the regulation of body weight,” said Erritzoe, indicating that obesity may in the future be treatable with drugs.

Serotonin is a molecule synthesized by specific brain cells (neurons), and it serves as a messenger molecule between neurons, a so-called neurotransmitter, explained Erritzoe. It is released by one neuron and received by receptors sitting on another neuron. Serotonin is involved in the regulation of many important physiological functions such as mood, sleep, sexuality, hormone secretion and appetite. Abnormalities in serotonin’s transmitter system play an important role in many disorders, including the biochemistry of depression, migraine, bipolar disorder, anxiety and eating disorders.

PET scans were performed on 76 healthy humans, of whom 47 were normal weight (body mass index between 19.2 and 24.9) and 29 were overweight (BMI between 25.1 and 34.7). “The relationship between the brain’s 5-HT2A receptors and body weight will prompt further investigation to explore whether this is a trait or rather a state marker of obesity,” said Erritzoe. “Our study emphasizes the importance of conducting large-scale PET studies in healthy people to address complex questions with molecular brain imaging,” he indicated.

“Our study deals with only moderately overweight people,” said Erritzoe, who explained that investigation should continue on whether 5-HT2A receptors are also involved in extreme under- or overweight people. “An interventional study where people are investigated before and after an intended weight loss would reveal whether the 5-HT2A receptor binding can be modified through weight loss,” he added. “In addition, trials involving different drug treatments aimed at the 5-HT2A receptor could reveal whether weight loss could be achieved through pharmacological effects on the receptor,” he noted.

Abstract: D. Erritzoe, V.G. Frokjaer, H. Arfan, S. Haugbol, H. Pinborg, C. Svarer, O.B. Paulson and G.M. Knudsen, Neurobiology Research Unit, N9201, Rigshospitalet, Copenhagen, Denmark, and J. Madsen, Nuclear Medicine Department, Rigshospitalet, Copenhagen, Denmark, “Overweight Associated With Increased Serotonin 2A Receptor Binding in Humans,” SNM’s 53rd Annual Meeting, June 3–7, 2006, Scientific Paper 18