OHSU Researchers Show Brain Receptor May Control Obesity

08/08/00    Portland, Ore.

Scientists at Oregon Health Sciences University's Vollum Institute have found a new receptor site in the brain of mice that causes them to become obese by storing fat and expending less energy than normal mice. In a study that will be reported in the September 2000 issue of Endocrinology (Volume 141, Number 9), a journal of The Endocrine Society, Roger Cone, Ph.D., a senior scientist at Vollum Institute and Associate Professor of cell and developmental biology in the OHSU School of Medicine, and Andrew Butler, Ph.D., a senior fellow at the Vollum Institute, discovered that the Melanocortin-3 receptor (MC3-R) is involved in the regulation of body weight.

The researchers discovered that mice lacking the MC3-R have 50 percent more fat than normal mice without any increase in food intake. In addition, when given an exercise wheel, the mice that lacked MC3-R exercised approximately half the amount of normal mice. Finally, when the amount of fat was increased in their diet, the mice without MC3-R appeared to burn more carbohydrates for fuel, which may have allowed them to more efficiently store fat in adipocytes, or fat cells. Scientists are now working to determine if mutations in MC3-R in humans are responsible for genetic predisposition to obesity.

"This new receptor site is different from past findings because this site appears to cause obesity by making the animal store fat more efficiently," said Dr. Cone. "Obesity in humans is commonly associated with increased food intake, but this new data shows it is theoretically possible to become obese due to genetic changes that increase the efficiency with which calories are stored in the form of fat."

Scientists have already discovered that energy stored in the form of fat is controlled and balanced internally. The brain continually adjusts food intake and energy expenditure to maintain constant levels of fat, similar to the way that a thermostat in a house maintains constant temperature. Previous research by Dr. Cone and other scientists also found that blocking a related neuropeptide receptor, called the MC4-R, in the brains of mice stimulates food intake and ultimately causes obesity.

"This new research helps us better understand the genetic determinants of obesity, metabolism and the regulation of fat mass, which have been poorly understood in the past. In the future, this type of research will lead to new drugs to treat obesity and will help endocrinologists and other doctors who treat patients suffering from obesity to better manage the condition," said Endocrine Society President-Elect, William Crowley.

Dr. Cone's work was funded by grants from the National Institutes of Health and Neurocrine Biosciences Inc. of San Diego. Based in Bethesda, Maryland, The Endocrine Society consists of more than 9,000 scientists and physicians in more than 80 countries. Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Together, these physicians, scientists, educators, nurses, and students who make up the organization's membership, represent all basic, applied, and clinical interests in endocrinology.