Repeated jet lag found to increase risks of obesity and liver cancer

People experiencing chronic jet lag could develop obesity and liver diseases including liver cancer, reports a recent study. Variable sleep timings and exposure to light may result in excessive production of bile acids, which could result in cancer.

A team of researchers from Baylor College of Medicine (BCM) has found that chronic jet lag may result in obesity and liver diseases including liver cancer.

David Moore, the lead author of the study from BCM said that the incidence of liver cancer is increasing worldwide in recent years and it is also observed lately that individuals suffering from fatty liver disease develop liver cancer directly skipping intermediate steps like cirrhosis.

In the study conducted in mice in BCM accoiate professor Loning Fu's lab, it was observed that mice that experienced chronic jet lag developed liver cancer in a pattern similar to obese humans, noted Moore.

The central circadian clock of the brain resets when a person is exposed to light. The clock is disturbed when a person is awake at night, works in night shifts or travels to countries with different time zones. Eventually, the other tissues in the body are disturbed, which affects the central clock altogether.

The researchers tested mice fed with a healthy diet and modeled a jet lag experiment by switching the lights on and off at varying time schedules every week. Doing so, it was observed that the mice gained weight and were found to have developed fatty liver disease. Some test animals also developed chronic inflammation in liver, which resulted in liver cancer.

Liver metabolism was greatly affected in jet lagged mice, which resulted in accumulation of fat in liver. The production of bile acids meant for digestion of fat was also found to have increased. It is to be noted that a number of studies conducted earlier have established an association between liver cancer and high levels of bile acids in liver in humans.

Every time the circadian clock is disturbed, two receptors are activated to regularize the body's metabolism. FXR receptor that controls the amount of bile acids in liver was found to be lacking in the jet-lagged mice. Eventually, the mice that ended up having high levels of bile acids developed liver cancer. However, mice lacking CAR, a receptor responsible for breaking down of bile acids, did not develop liver cancer.

The researchers noted that the two receptors are also found in humans, making the condition applicable to them as well. Further research on the issue is needed to develop treatment options to manage the receptors in case of jet lag and sleep disruption for preventing liver cancer, noted the investigators.

"To us, our results are consistent with what we already knew about these receptors, but they definitely show that chronic circadian disruption alone leads to malfunction of these receptors," Fu said, as reported by Eurekalert. "And thus, maintaining internal physiological homeostasis is really important for liver tumor suppression."

The study was published in the journal Cancer Cell on Nov. 23.

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