US researchers have discovered that a high fat diet can change a mammal's body clock and thereby disrupt a range of behavioural and physiological processes, including those controlled by genes that switch on and off at certain times to keep the body's metabolism, storage and use of energy in balance.

The study is published in the journal Cell Metabolism and was carried out by researchers at Northwestern University in Evanston, Illinois.

The researchers found not only that the high fat diet changed the sleep patterns of laboratory mice, but it also changed the way genes were expressed in their brains.

The body's circadian or internal clock regulates not only the behavioural patterns of daily life, sleep and eating, but it also controls many internal processes such as metabolism, storage, distribution and usage of energy. The balancing of these processes is called homeostasis.

Previous research has found that changing the internal molecular clock structure using genetic technology can seriously disrupt the signals used to control metabolism. Many metabolic systems are also cyclical in nature, and this may impact the timing of when genes switch on and off.

In fact, the team at Northwestern, led by Dr Joe Bass, assistant professor of medicine and neurobiology and physiology at Northwestern and head of the division of endocrinology and metabolism, has been working in this field for some time and has published a range of papers showing, for example, that a faulty body clock, or one that is out of step with its environment, can disrupt metabolism and increase the risk of diabetes and obesity.

The team also knew that genetic mutation was unlikely to be the most common reason for a disrupted body clock, so they turned to other questions. What else might be doing this? They decided to investigate different ways in which the body's energy balance is affected, and one way is to start with where the energy comes from in the first place - food.

Bass said their question was simple: could food itself alter the body clock? And the answer they discovered was, yes, it could. Changing food affects timing.

They found that feeding mice on a high-fat diet led to changes in their regular sleep/wake cycle behaviour, causing them to eat when they would have been sleeping. All the additional calories were being consumed when the mice should have been resting, said Bass.

"For a human, that would be like raiding the refrigerator in the middle of the night and binging on junk food," explained Bass.

It becomes a vicious cycle of disrupted body clock leading to more bad eating habits which in turn disrupts the body clock even more.

"Timing and metabolism evolved together and are almost a conjoined system," explained Bass. There is a delicate balance between the two.

The body clock is a molecular system found everywhere in the body, in the brain, the muscles, lungs, liver, heart, even helping to balance the body's fluids, so kidneys, bladder, circulation, as well as digestion, are involved. The clock works on a near 24 hour cycle.

The researchers showed that the high fat diet also led to changes at the genetic level, in the timing of genes switching on and off. This affected when chemicals coded by the genes were produced, some of which control time sensitive energy processes in the hypothalamus, liver, and fat tissue.

Bass and colleagues took genetically identical laboratory mice and fed them on a regular diet for 2 weeks. For the next 6 weeks they split them into two separate groups. One group stayed on the regular diet and the other group was given a high calorie, high fat diet. 45 per cent of the calories in the high fat, high calorie diet came from fat.

The mice were kept in the dark so that only body clock changes regulated their wake/sleep cycle as opposed to environmental light levels.

After 2 weeks, the high fat diet group abruptly changed their normal eating and sleeping cycle. They were eating during their normal sleep time, which for a mouse is during the day. The other group that stuck to the regular diet did not show these changes.

The key point, said Bass, is not that they were eating more at regular meals, but that they were consuming all their calories when they should have been sleeping.

The researchers concluded that their experiment showed that a high fat diet can change a mammal's body clock and therefore its regulation of essential physiological processes.

"High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice."
Akira Kohsaka, Aaron D. Laposky, Kathryn Moynihan Ramsey, Carmela Estrada, Corinne Joshu, Yumiko Kobayashi, Fred W. Turek, and Joseph Bass.
Cell Metabolism, Vol 6, 414-421, 07 November 2007.
doi:10.1016/j.cmet.2007.09.006

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Written by: Catharine Paddock