Mitochondrial Protein Maintains Appetite During Fasting

Researchers at Yale School of Medicine have found that a thyroid hormone in the brain is linked to the “uncoupling” protein UCP2, which can maintain appetite during periods of fasting so that the body is ready to eat when food is reintroduced.

Published in the January issue of Cell Metabolism, the study was conducted by observing the behavior of mice that fasted for 24 hours. The researchers, led by Sabrina Diano, associate professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences and Neurobiology, found that during fasting there was an increase in UCP2 as well as an increase in the type 2-deiodinase enzyme that stimulates thyroid hormone production in the hypothalamus.

When the mitochondrial protein UCP2 was activated due to fasting, the number of mitochondria increased in the neurons, which increased excitability in the brain cells that are critical in initiating eating. The researchers also showed that “knock-out” mice that lacked UCP2 or type 2 deiodinase ate less after fasting.

“We found that a cellular mechanism that is similar to that involved in generating body heat is also present in the brain,” said Diano. “UCP2 appears to be an important player in regulating neuronal function associated with feeding. We would like to conduct further studies to learn whether this mechanism may indeed have thermogenic consequences in the brain and if so, whether selective cooling or heating of the hypothalamus could affect metabolism.”

Diano said the mitochondria in the brain appear to be important players in regulating neuronal function associated with feeding behavior and energy expenditure. Mitochondrial dysfunction in peripheral tissues such as liver and muscle has been shown to play a critical role in insulin resistance in diabetes. This study indicates that brain mitochondrial dysfunction may also play a critical role in the etiology of obesity and diabetes.

The study was funded by grants from the National Institutes of Health and a grant from the Juvenile Diabetes Research Foundation to Diano.

Other authors on the study were Anna Coppola, Zhong-Wu Liu, Zane B. Andrews, Eric Paradis, Marie-Claude Roy, Jeffrey M. Friedman, Daniel Ricquier, Denis Richard, Tamas L. Horvath and Xiao-Bing Gao.

Citation: Cell Metabolism, Vol. 5, Issue 1, 21-33 (January 2007)

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Karen N. Peart: karen.peart@yale.edu, 203-432-1326