Gene Connects Biological Clock to Weight Regulation
Scientists report a new link between a gene that controls the body's biological clock and weight gain.
Our body's daily rhythms are synchronized with the sun and coordinated by cells in the brain called a circadian clock. The body's circadian clock regulates our sleep, body temperature, eating habits and activity levels. While a region of the brain operates as the master biological clock, many tissues in our body have their own clocks. The system is complex, with central clock genes directing the body's rhythms, deciding which proteins are expressed in which tissues at different times of the day. When our biological clock is disrupted, it can cause sleep disorders and a host of other problems, including obesity, depression, heart disease, high blood pressure and diabetes. Researchers at the University of Virginia and the Medical College of Wisconsin have found a new link between a circadian clock gene called Nocturnin and obesity.
Dr. Carla Green and Dr. Joseph Besharse, the study's lead investigators, and their colleagues were interested in following up on previous studies that suggested a key role for Nocturnin in controlling the daily rhythmic pattern of gene expression. With support from NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Eye Institute (NEI) and National Institute of General Medical Sciences (NIGMS), the researchers created mice that were genetically altered to lack the gene for Nocturnin and compared them to normal mice.
The group reported in the May 17, 2007, online edition of the Proceedings of the National Academy of Sciences that the genetically altered mice appeared to have normal circadian rhythms. There were no obvious differences between the normal and genetically altered mice when the mice were fed a standard diet. Surprisingly, however, when fed a high-fat diet, the mice lacking Nocturnin stayed slim while the normal mice almost doubled their weight. The Nocturnin-deficient mice also failed to accumulate fat in their livers and bellies, unlike their normal counterparts. The researchers showed that resistance to weight gain in the genetically altered mice was not caused by decreased food intake, increased activity or an increased metabolic rate.
The scientists found that the livers of the slim Nocturnin-deficient mice had lower expression levels of genes involved in fat production and storage in comparison to their obese counterparts. This result suggests that mice lacking Nocturnin may fail to gain weight from the high-fat diet because they are unable to absorb or process the fat from their food.
This study reveals an underlying molecular link between our biological clock and the regulation of body weight. Exploring this connection is critical in light of rising obesity rates and the health burden this brings.
--by Deborah Stewart, Ph.D.-National Institute of Health Column
The NIH-the nation's medical research agency-includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.