Jet lag may up liver cancer risk: study

Repeated jet lags may increase obesity-related liver disease as well as risk of liver cancer, a new study has warned.
When we are exposed to light, our body's central circadian clock in the brain resets.
When we constantly travel through different time zones, work night shifts, or push ourselves to stay awake at the regular sleep time, our central clock is being chronically disrupted, said researchers from Baylor University in the US.
This disruption also extends to clocks in other tissues that are controlled by the central clock, they said.
By changing the times the lights went on and off during the night each week, the researchers modelled the effects of chronic jet lag in normal mice who were fed a healthy diet.

They found that the mice gained weight and fat, and developed fatty liver disease, which progressed to chronic inflammation and eventually liver cancer in some cases.

The jetlagged mice lost normal control of liver metabolism.
This included not only the buildup of fat, but also increased production of bile acids, which are produced by the liver to help us digest our food.
Earlier studies have linked high bile acid levels to liver cancer, not only in mice but also in humans.
The researchers found that circadian clock disruption activated two nuclear receptors that help regulate liver bile acid metabolism.
Jetlagged mice lacking a receptor called FXR, which keeps bile acid level in the liver within a normal physiological range, had higher bile acid levels and much more liver cancer.

Mice lacking a receptor called CAR that regulates bile acid breakdown and is also known to promote liver cancer, did not get any liver tumours.
In humans, these receptors work in a similar manner. Scientists did not directly study jetlag in humans.
However, there is evidence that sleep disruption increases both fatty liver disease and liver cancer risk in humans, and they hypothesise that lifestyle changes that generate chronic jet lag can also disrupt the body's internal homeostasis and increase liver cancer risk in humans.
"Liver cancer is on the rise worldwide, and in human studies we have now seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis," said David Moore, professor at Baylor University.

"We knew we needed an animal model to examine this connection, and studies in the Fu Lab found that chronically jet-lagged mice developed liver cancer in a very similar way as that described for obese humans," said Moore.
The study appears in the journal Cancer Cell.