Gene Plays Role in Weight Gain, Study Shows

A gene involved in circadian rhythms was found to play a role in weight gain in mice, according to a study led by Joseph C. Besharse, PhD, Marvin Wagner Professor and Chairman of Cell Biology, Neurobiology and Anatomy, and Carla Green, PhD, Associate Professor of Biology at the University of Virginia.

The gene, called Nocturnin, normally functions at night. In the study, the researchers deleted Nocturnin in a group of mice to investigate the gene's function. The Nocturnin-deficient mice were resistant to the development of obesity and fatty liver disease. They did not gain weight when fed a high-fat diet, compared to a control group of normal mice whose weight doubled on the same high-fat diet. The finding was published online in the Proceedings of the National Academy of Sciences USA.

"This paper adds an important new twist to a recent body of evidence that circadian rhythms play an important role in the control of metabolism and energy balance," said Dr. Besharse. "This work has important health implications because diet-related obesity and Type II diabetes are a growing health concern in Western society."

Circadian rhythms, such as our awakening and sleeping routines, are controlled by mechanisms that act like internal clocks. These near 24-hour rhythms affect behavior, physiology and metabolism.

The Nocturnin gene was originally discovered in Dr. Besharse's laboratory more than a decade ago through the work of Dr. Green, who was then a post-doctoral research trainee.

The next step is to understand the molecules controlled by Nocturnin in mice. Further work on how Nocturnin and other components of the internal clock control metabolism could lead to novel therapies for metabolic diseases, such as obesity and Type II diabetes.

The targeted deletion of the Nocturnin gene necessary for this work was done by Dr. Besharse's laboratory using technology and facilities of the Center for Human and Molecular Genetics at the Medical College and was funded by the National Institutes of Health.

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