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April 9, 2012
Researchers Discover Powerful Link Between Circadian Rhythms and Metabolism

The discovery of a major gear in the biological clock that tells the body when to sleep and metabolize food is leading to a new understanding on metabolic disorders, including diabetes.

Scientists at the Salk Institute for Biological Studies, led by Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, showed that two cellular switches found on the nucleus of mouse cells, known as REV-ERB alpha and REV-ERB beta, are essential for maintaining normal sleeping and eating cycles and for metabolism of nutrients from food.

The findings, reported March 29 in Nature, describe a powerful link between circadian rhythms and metabolism and suggest a new avenue for understanding disorders of both systems, including jet lag, sleep disorders, obesity and diabetes.

“This fundamentally changes our knowledge about the workings of the circadian clock and how it orchestrates our sleep-wake cycles, when we eat and even the times our bodies metabolize nutrients,” says Evans.

Nurses, emergency personnel and others who work shifts that alter the normal 24-hour cycle of waking and sleeping are at much higher risk for a number of diseases, including metabolic disorders such as diabetes. To address this, scientists are trying to understand precisely how the biological clock works and uncover possible underlying mechanisms that could adjust the circadian rhythm in people with sleep disorders and circadian-associated metabolic disorders.

In mammals, the circadian timing system is orchestrated by a central clock in the brain and subsidiary clocks in most other organs. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior.

Scientists knew that two genes worked together at the core of the clock’s molecular machinery to activate the network of circadian genes. In this way, the genes acts like the accelerator on a car, activating genes to rev up our physiology each morning so that we are alert, hungry and physically active.

The scientists also found that the REV-ERBs control the activity of hundreds of genes involved metabolism, including those responsible for controlling levels of fats and bile. When REV-ERB alpha and REV-ERB beta are turned off, there are high levels of fat and sugar in the blood -- common problems in people with metabolic disorders.

“This explains how our cellular metabolism is tied to daylight cycles determined by the movements of the sun and the earth,” says Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory and co-author on the paper. The researchers suggest that a method must be found to leverage this mechanism to fix a person’s metabolic rhythms when they are disrupted by travel, shift work or sleep disorders.

Gaining Weight? Check Your Internal Time

Recent findings suggest that circadian rhythms are intricately tied to weight gain. When Carla Green and her collaborators at the University of Virginia fed high-fat diets to mice with and without a protein involved in circadian rhythms, they found that the mice lacking the protein gained only a modest amount while the mice with the protein nearly doubled their body weight. The findings suggest that circadian rhythms regulate metabolic processes involved in diet-induced weight gain.

Clock in a Box

Carl Johnson and colleagues at Vanderbilt University have reconstituted a circadian clock in vitro using three proteins. The synthetic clock follows a 24-hour rhythm, and it maintains this cycle over a range of temperatures—a defining, but poorly understood characteristic of circadian rhythms. The advance offers an unprecedented opportunity to study the mechanisms of internal clocks, the role of temperature in regulating daily cycles, and even the evolution of human circadian rhythms.

Single Change Starts the Clock

In a surprising finding, Paolo Sassone-Corsi of the University of California-Irvine and colleagues found that a single amino acid change in a protein triggers a chain of genetic events involved in internal timekeeping. If the modification is impaired, it could disrupt the cascade and serve as the underpinning of circadian rhythms-related ailments. The amino acid also could be a novel target for drug compounds regulating body clocks.

Food Plays a Role

While many experts argue that light has the strongest influence on how that clock is oriented, some evidence suggests that what and when we eat might play an equally, if not more important, role. Now, new study findings by Dr. Steven McKnight of the University of Texas Southwest Medical Center in Dallas and colleagues provide further evidence that food has a significant effect on our internal clock, or circadian rhythm.

Regardless of whether food or light has the upper hand, more and more evidence suggests that people who travel to a new time zone should adopt the meal schedule of the new place to help combat jet lag, McKnight told Reuters Health.

If an airline offers a large meal that matches the place you just left but not where you are going, the researcher suggested opting out, and trying to train your stomach to adopt to your destination's time zone. "Begin to have your feeding cycle on that new daylight schedule that you're going to be in," McKnight advised.

April McCarthy is a community journalist playing an active role reporting and analyzing world events to advance our health and eco-friendly initiatives.


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