Is being overweight all in the brain?

PET study links obesity to serotonin receptor, suggesting possibility of curbing appetite with future drugs, note findings issued at SNM's 53rd Annual Meeting June 37 in San Diego

SAN DIEGO, Calif.--By using positron emission tomography (PET) 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. Their findings were presented at SNM's 53rd Annual Meeting June 37 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.

Obesity among adults has risen significantly in the United States--cutting across all ages, racial and ethnic groups and gender. 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. These increasing rates have profound implications for health, because being overweight or obese increases the risk of many diseases and health conditions, including coronary heart disease, high blood pressure, diabetes, stroke and some cancers.

"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.

PET is a safe, painless biological imaging exam that is used to detect the presence and extent of cancer, cardiovascular disease, neurological conditions and other physiological problems. While other imaging techniques use "photographs" to provide anatomical information, PET images the biological processes taking place within the body, producing functional information that can be used for diagnosis, evaluation and therapy of disease. PET uses very small amounts of radioactive materials targeted to specific organs, bones or tissues. These radiotracers, attached to simple compounds such as glucose, are administered to a patient and then detected or "traced" by a special type of camera that works with computers to provide precise pictures of the area of the body being imaged.

"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.

This research points to a certain type of brain receptor as influencing a person's weight, said Satoshi Minoshima, SNM's Scientific Program Committee neurosciences vice chair. "It points to the possibility of treating obesity by developing neurological drugs as opposed to taking diet pills and undergoing stomach stapling procedures," added the professor of radiology and bioengineering and vice chair for research in the department of radiology and head of the Primate PET Imaging Suite at the University of Washington in Seattle.

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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 37, 2006, Scientific Paper 18.

About SNM

SNM is holding its 53rd Annual Meeting June 37 at the San Diego Convention Center. Research topics for the 2006 meeting include molecular imaging in clinical practice in the fight against cancer; the role of diagnostic imaging in the management of metastatic bone disease, metabolic imaging for heart disease, neuroendocrine and brain imaging, new agents for imaging infection and inflammation, and an examination of dementia, neurodegeneration, movement disorders and thyroid cancer.

SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed resource in the field; sponsor research grants, fellowships and awards; host the premier annual meeting for medical imaging; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced--and continue to explore--biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org.


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