Diets that are high in fat can shift the timing of the body’s internal clock, researchers report in the November issue of Cell Metabolism, a publication of Cell Press.
The researchers found that mice fed a fatty diet quickly develop changes in their normal activity patterns. The animals begin eating more during the day, when mice—being nocturnal—are supposed to be asleep. They also exhibit changes in the molecular components of the circadian clock and in important aspects of metabolic chemistry.
“We found that, as an animal on a high-fat diet gains weight, it eats at the inappropriate time for its sleep/wake cycle. All of the excess calories are consumed when the animal should be resting,” said Joe Bass of Northwestern University. “For a human, that would be like raiding the refrigerator in the middle of the night and binging on junk food.”
“You can begin to see changes in the animals’ daily habits very rapidly—within a matter of days,” he added.
In recent years, scientists have been paying increasing attention to the connection between the circadian network and metabolism. For instance, Bass’s group and others have recently uncovered a link between these two processes by demonstrating that Clock mutant mice overeat and become obese. While the effects of the molecular circadian clock on metabolic processes have now been well documented, Bass said, much less is known about how metabolic processes, such as nutrient status, may alter the circadian clock.
In the new study, the mice received 45 percent of their calories from fat. For humans, it’s recommended that no more than 30 percent of calories come from fat. After two weeks on the high-fat diet, the animals showed significant behavioral changes. Their daily sleep/wake cycle grew longer, suggesting that the central mechanism in the brain that controls the timing of activity and rest had been affected. That observation was made in animals kept in constant darkness, so that their behavior reflected only the workings of their internal clocks.
The researchers then examined the animals’ activity patterns when kept in 12 hours of light and 12 hours of darkness. As expected, mice fed a regular diet maintained a robust daily rhythm of food intake and activity throughout the entire experiment, with most of their activity and feeding, about 80 percent, occurring during the dark period. As early as the first week on the high-fat diet, the mice began consuming more food when the lights were on.
In addition, the researchers found, mice on the high-fat diet displayed altered activity of key genes that control the roughly 24-hour circadian rhythm. These clock-controlled metabolic genes are expressed in parts of the brain, as well as in the liver and fat tissue. The high-fat diet suppressed the activity of the core clock genes, Bass said.
“It’s not only activity and feeding that shifts, but also the molecular processes involved in metabolism,” Bass said. “The changes appear to be global. The clock is an ancient mechanism for matching behavior to changes in the external environment that vary in accordance with the rotation of the earth, and the cycle of light and darkness. We now show that the clock is also clearly influenced by the composition of the diet.”
The researchers include Akira Kohsaka, of Northwestern University, in Evanston, IL, and Evanston Northwestern Healthcare Research Institute and Department of Medicine, Evanston Hospital, Evanston, IL; Aaron D. Laposky, of Northwestern University, in Evanston, IL; Kathryn Moynihan Ramsey, of Northwestern University, in Evanston, IL, and Evanston Northwestern Healthcare Research Institute and Department of Medicine, Evanston Hospital, Evanston, IL; Carmela Estrada and Corinne Joshu, of Northwestern University, in Evanston, IL; Yumiko Kobayashi, of Evanston Northwestern Healthcare Research Institute and Department of Medicine, Evanston Hospital, Evanston, IL; Fred W. Turek, of Northwestern University, in Evanston, IL; and Joseph Bass, of Northwestern University, in Evanston, IL, and the Evanston Northwestern Healthcare Research Institute and Department of Medicine, Evanston Hospital, Evanston, IL.
Journal
Cell Metabolism