Researchers in the US studying mice found that they could shift the animals’ circadian rhythm or body clock by controlling food availability, suggesting that changing patterns of mealtimes might help humans adjust their body clock too, for instance to cope with jet lag or get used to shiftworking.

The study was conducted by researchers at Beth Israel Deaconess Medical Center (BIDMC), in Harvard Medical School, Boston, and is published online today, 23rd May, in the journal Science.

The primary biological clock of animals is controlled by a group of cells in the brain’s hypothalamus that is known as the suprachiasmatic nucleus (SCN). The SCN scans the visual system for signals about whether it is light or dark and passes that information to the dorsomedial nucleus (DMH), also in the hypothalamus. The DMH organizes when the body is asleep and when it is awake, and the ups and downs of hormones and other bodily functions to suit.

The system works well when food is plentiful; animals’ body clocks or circadian rhythm follows the daily cycle of light and dark. But when food availability is disrupted, for instance if it becomes available only during their normal sleep period, animals are able to shift their circadian rhythm to a new pattern so as to be awake (and presumably alert) when food is available.

Senior author Dr Clifford Saper, who is Chairman of the Department of Neurology at BIDMC, and colleagues, decided to investigate the underlying mechanisms whereby a “food-clock” appeared to override the more usual “light-clock” as a primary way to regulate the circadian rhythm.

A significant obstacle would be the fact that some of the cells of the SCN called “oscillator cells” also exist elsewhere in the brain and other places like the stomach and liver, and these also play a role is establishing the circadian rhythm.

Saper said that:

“Dissecting this large intertwined system posed a challenge.”

So they simplified the task by using genetically engineered mice that had a key biological clock gene, BMAL1, switched off. They then used a viral vector to introduce switched on BMAL1 genes into selected parts of the brain one step at a time.

When the researchers injected the BMAL1 vector into the SCN part of the hypothalamus, they were able to restore the mice’s circadian rhythms in response to light and dark changes, but not to food availability patterns.

But when they injected the BMAL1 vector into the DMH part of the hypothalamus, they were able to restore the mice’s circadian rhythms in response to food availability patterns, but not to light and dark changes.

The researchers concluded that:

“These results demonstrate that the dorsomedial hypothalamus contains a BMAL1-based oscillator that can drive food entrainment of circadian rhythms.”

So using this stepwise method the researchers found the food-clock in the DMH, as Saper explained:

“We discovered that a single cycle of starvation followed by refeeding turns on the clock, so that it effectively overrides the suprachiasmatic nucleus and hijacks all of the circadian rhythms onto a new time zone that corresponds with food availability.”

The discovery could help travellers and shift workers, said Saper:

“Modern day humans may be able to use these findings in an adaptive way,” he said, explaining that it takes the average person about a week to adjust to an 11-hour shift in time zone, as someone who travels from the US to Japan, for example, will know, “because the body’s biological clock can only shift a small amount each day”.

But by the end of the week, it’s probably time to fly home again, so wouldn’t it be useful to have a way of speeding up the adaptation process so the body gets used to the new time zone more quickly?

Saper suggests that by changing the timings of meals, travellers might be able to trigger the second food-clock into action and help their bodies overcome jet lag more quickly. How to do this? Saper suggests:

“A period of fasting with no food at all for about 16 hours is enough to engage this new clock.”

“So, in this case, simply avoiding any food on the plane, and then eating as soon as you land, should help you to adjust – and avoid some of the uncomfortable feelings of jet lag,” he adds.

“Differential Rescue of Light- and Food-Entrainable Circadian Rhythms.”
Patrick M. Fuller, Jun Lu, and Clifford B. Saper.
Science Vol. 320. no. 5879, pp. 1074 – 1077.
Published online on 23 May 2008.
DOI: 10.1126/science.1153277

Click here for Abstract.

Sources: Science abstract, Harvard press release.

Written by: Catharine Paddock, PhD