Cause of Obesity in Shift Workers May All Be a Matter of Timing

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University of Pennsylvania researchers believe that their study of mice that eat their meals at the wrong time of the day may explain why shift workers and patients with sleep disorders tend to be overweight or obese.

In a new study published in the journal Nature Medicine, researchers have uncovered a genetic/molecular pathway of mammalian internal clocks that when disrupted can cause increased fat storage and thereby excessive weight gain.

Scientists have recently looked at a mammalian clock gene in fat cells that is known under two names: "Arntl" and "Bmal1." The researchers found that when mice carry a deletion of the clock gene Arntl/Bmal1 in their fat cells, that the mice do two things: they shift their normal eating pattern from nighttime to daytime…and they become obese. This deletion of the Arntl/Bmal1 gene results in a broken molecular clock that disrupts the brain-body timing involved in eating.

However, this weight gain from eating at the wrong time of the day is not due to eating more calories than normal. In addition, normal mice that do not carry the clock gene deletion will become obese as well if their normal nocturnal eating time is artificially changed.

According to the Penn researchers, “…a relatively modest shift in food consumption into what is normally the rest period for mice can favor energy storage,” says lead author Georgios Paschos PhD. “Our mice became obese without consuming more calories.”

The researchers propose that the weight gain seen in the Arntl/Bmal1 mice is due to the disruption of their master internal clock, that among other things, directly affects cellular metabolism. The internal clock is an area of the brain called the suprachiasmatic nucleus (SCN), which is located in the hypothalamus and is responsible for regulating a 24-hour cycle by producing a signal keeps the rest of the body on its normal time schedule. As it turns out, while the SCN is the master clock, there are minor internal clocks within non-brain cells in the body that can influence the timing of the master clock in the brain.

According to a news release issued by Penn Medicine, the researchers liken this to a percussionist in an orchestra that is able to influence a conductor’s rhythm.

“While we have long known that peripheral clocks have some capacity for autonomy—the percussionist can bang the drum without instructions from the conductor —here we see that the orchestrated behavior of the percussionist can, itself, influence the conductor,” explains co-author and the study’s lab director Garret A. FitzGerald.

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The authors explain that eating behavior is normally controlled by clock signals from specific cells such as fat cells (the percussionist) that directs the hypothalamus (the conductor) to either promote eating or suppress appetite. However, if the fat cells have a broken clock such as the deletion of the Arntl/Bmal1 gene seen in the mutant mice, then the hypothalamic rhythm is thrown off leading to eating at the wrong time of the day, which in turn derails normal fat metabolism and leads to storage rather than burning of fat.

One example of fats not being metabolized appropriately was the researcher’s discovery that the unsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the Arntl/Bmal1 deleted mice were not released into the blood as they should be, but remained stored in fat cells.

However, when the Arntl/Bmal1 deleted mice were fed EPA and DHA, their normal metabolism was restored.

“To our amazement, we were able to rescue the entire phenotype—inappropriate fatty acid oscillation and gene expression in the hypothalamus, feeding pattern and obesity—by supplementing EPA and DHA to the knock-out animals,” notes Paschos.

The researchers concluded that their findings indicate that fat cell clock molecules play an important role in the regulation and the timing of eating by communicating with the hypothalamus. This communication ultimately affects stored energy and body weight and could be a likely reason why shift workers or individuals with sleep disorders find themselves gaining weight without consuming extra calories.

Image Source: Courtesy of MorgueFile

References:

“Obesity in mice with adipocyte-specific deletion of clock component Arntl” Nature Medicine (Published online 11 November 2012); Georgios Paschos, PhD. Et al.

Penn Medicine news release

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