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Imaging study of rodents' brains called a first in obesity research (1-31-00)

A spoonful of sugar helps the medicine go down, but what else does it do? How does the brain respond when the body takes in sugar?

Researchers at The University of Texas Health Science Center at San Antonio arenít actually giving spoonfuls of sugar to laboratory rats, but they are administering glucose and monitoring the brain activity of the rats immediately afterward. By using an imaging technique called functional magnetic resonance imaging (fMRI), scientists at the Health Science Centerís Research Imaging Center (RIC) expect to glean more insight into the brainís response to energy intake. They also seek to understand why only some animals and humans develop obesity and diabetes.

They are concentrating their attention on the hypothalamus, an essential neural regulatory center in the brain. The hypothalamus is intimately involved in the maintenance of basic life processes such as feeding and drinking. In an article published in the January issue of Magnetic Resonance in Medicine, the scientists report that they are the first to use fMRI in rats to examine the response of the hypothalamus to glucose administered into the abdominal cavity. Functional MRI of the brain is a non-invasive technique that records the brainís "dynamic activity" in response to both internal and external stimuli.

The scientists are building on their earlier study, published last September in the journal Diabetes, that used fMRI to document significant differences in the hypothalamic response between lean and obese humans following oral glucose intake.

"This rat study was undertaken to determine the feasibility of using an animal model to perform fMRI experiments in the fields of obesity and diabetes," said Srikanth Mahankali, M.D., postdoctoral fellow at the Research Imaging Center and lead author of the Magnetic Resonance in Medicine article. "Such experiments are impractical to perform in humans because they require the administration of appetite-regulating hormones, such as leptin and neuropeptide Y, which are involved in the regulation of feeding behavior."

While leptin decreases appetite, neuropeptide Y increases it.

"Leptin and neuropeptide Y cannot be administered safely to humans, which makes the rat model invaluable in designing future fMRI experiments involving obesity and diabetes," said Jia-Hong Gao, Ph.D., associate professor of radiology and chief of the MRI Division at the Research Imaging Center. Both the human and animal fMRI studies were conducted under his supervision. Data acquisition for the rat study was accomplished by Yonglin Pu, M.D., Ph.D., assistant professor of radiology at the RIC.

In the present experiment, six male, non-diabetic rats of varying age and weight were injected with glucose into the abdominal cavity. "Though all the rats showed an appetite-inhibiting response in the hypothalamus after glucose injection, the magnitude and rate of response varied with the age and weight of the animals, suggesting that these were key elements in modulating feeding behavior," Dr. Gao said.

The earlier human study showed a difference in hypothalamic function in the brains of 10 lean vs. 10 obese individuals. A quicker and more sustained response by the hypothalamus was noted in lean patients after oral glucose administration as compared to the response observed in obese individuals. No diabetic patients were enrolled.

The human study was a collaborative effort between Dr. Gao at the RIC and Ralph DeFronzo, M.D., chief of the Division of Diabetes in the Health Science Centerís Department of Medicine. Dr. DeFronzo also is a staff physician at University Hospital and the Audie Murphy Division of the South Texas Veterans Health Care System.

Contact: Will Sansom