A new mouse study suggests that a brain system that controls the sleep/wake cycle might also play a role in regulating appetite and metabolism. Mice with a mutation in a gene called "Clock," which helps drive circadian rhythm, ate significantly more and gained more weight.
A new mouse study suggests that a brain system that controls the sleep/wake cycle might also play a role in regulating appetite and metabolism. Mice with a mutation in a gene called "Clock," which helps drive circadian rhythm, ate significantly more and gained more weight. The finding could help explain why disrupted sleep patterns - particularly when combined with a high-fat diet - are associated with excessive weight gain and the onset of metabolic syndrome in some people, according to investigators supported by the National Institutes of Health (NIH).
The study, by Fred W. Turek, Ph.D., and Joseph Bass, M.D., Ph.D., of Northwestern University in Evanston, Ill., and others will be available at the Science Express website, http://www.sciencemag.org/sciencexpress/recent.shtml, on April 21, 2005. The National Institute on Aging (NIA), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supported this work. The NIA, NHLBI and NIDDK are components of the NIH at the U.S. Department of Health and Human Services.
At least 40 million Americans have chronic sleep problems, and an additional 20 million experience occasional sleeping problems. As many as 47 million Americans have metabolic syndrome, a cluster of conditions shown to increase a person's risk of heart disease and stroke. The National Cholesterol Education Program defines metabolic syndrome as having at least 3 of the following risk factors: high blood pressure, high glucose (sugar) levels which can indicate risk for diabetes, high triglyceride levels, low levels of good cholesterol, and a large waist.
Scientists have found that circadian rhythms (which control the sleep/wake cycle and other biological processes), hunger, and satiety are all regulated by centers within a brain structure called the hypothalamus. And previous studies in humans have suggested that disrupted sleep patterns may contribute to the development of obesity, diabetes, and metabolic syndrome.
In this latest work, Turek and his colleagues found that mutant mice were more active during times when rodents usually sleep. They also had less fluctuation in blood levels of leptin, a hormone that transmits a satiety signal to the brain. The researchers also found that Clock mutant mice had reduced levels of the hormone ghrelin within the hypothalamus, indicting that ghrelin may participate in the neuronal relay linking sleep, wakefulness, and appetite. Together, these alterations in neural and peripheral hormones suggest that a number of previously undetected brain circuits may exist that are common to sleep and eating.
The mice with a mutation in the Clock gene fed a regular diet gained about as much weight as normal mice that were fed a high-fat diet. The mice with a mutation in the Clock gene showed even greater weight gain and changes in metabolism when fed a high-fat diet. They developed a wide range of conditions associated with obesity, diabetes, and the metabolic syndrome, such as high levels of blood cholesterol, triglycerides, and glucose, and insulin resistance.
Andrew Monjan, Ph.D., of the NIA and Carl E. Hunt, M.D., director of the NIH National Center on Sleep Disorders Research, are available to discuss this study. To arrange an interview with Dr. Monjan, phone (301) 496-1752; for Dr. Hunt, phone (301) 496-4236.
NIA, NHLBI, and NIDDK are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. NIA information on conditions and diseases associated with aging is available at www.nia.nih.gov. NHLBI press releases and fact sheets, including information on obesity and sleep disorders can be found online at www.nhlbi.nih.gov. NIDDK information on weight control and nutrition can be found online at www.niddk.nih.gov.