TICK, TOCK: FAT DISRUPTS THE CLOCK

ScienceNOW Daily News
November 6, 2007

By Gretchen Vogel

A burger, fries, and a double fudge sundae for dessert is probably not the best recipe for a good night's sleep. Indeed, a new study shows that in mice, high-fat diets seem to disrupt the body's natural day and night rhythms. The work may help scientists understand why obesity, diabetes, and sleep disruption are often intertwined in human patients.

The body's daily rhythms are governed by the so-called circadian clock. The clock influences not only when we sleep but also when we get hungry and how efficiently our bodies process food. Several studies have shown that mutations in circadian clock genes can cause mice to gain weight (ScienceNOW, 21 April 2005). And humans deprived of sleep soon begin to overeat. But neurobiologist Joseph Bass and colleagues at Northwestern University in Evanston, Illinois, wondered if the connection worked the other way--whether diet could influence the clock.

The researchers put mice on a high-fat diet and measured their activity and eating behavior throughout the day and the night, comparing the rodents to mice on regular rations. After a week of noshing on high-fat chow, the mice were more restless during daylight hours, when most mice are sleeping. And they seemed to have the mouse equivalent of midnight munchies: Mice on high-fat diets consumed nearly a third of their food during the daytime hours, whereas the control mice consumed only about 20% of their calories during the day, the team reports in the 7 November issue of Cell Metabolism.

The high-fat diet also affected the animals' performance on a standard test of circadian rhythm, in which researchers keep animals in constant darkness and record their patterns of behavior. Mice usually have a characteristic daily activity cycle that lasts 23.6 hours. But after a week on high-fat chow, the experimental mice had a pattern about 20 minutes shorter than normal.

The behavioral changes were also reflected in the expression of circadian clock genes, brain hormones, and metabolic markers such as the levels of insulin, blood sugar, and fatty acids. In the high-fat munchers, the usual day-to-night peaks and valleys in clock gene expression in the brain, fat, and liver were flatter than normal, perhaps accounting for the animals' daytime wakefulness. Swings in insulin levels, on the other hand, increased. Other circadian-controlled hormones also showed abnormalities.

The results "clearly show that a controlled change in nutritional environment causes changes in circadian rhythms," says Mitchell Lazar, who studies obesity and metabolism at the University of Pennsylvania School of Medicine in Philadelphia. Neuroscientist Tamas Horvath of the Yale University School of Medicine says that if the effect is similar in humans, "your entire biological rhythm might be altered" by changes in diet. Horvath and Bass say that the next step is to tease out how the changes happen at a molecular level.