Jet_Lag

Jet Lag, Obesity & Pathways to Liver Cancer

Jet LagHepatocellular carcinoma, the most common type of liver cancer, has nearly tripled since 1980, and obesity related liver disease is one of the driving forces behind the increasing number of cases.  Baylor College of Medicine researchers are now examining other lifestyle factors that may affect your health. By using mice, the scientists have shown that repeated jet lag increases both obesity related liver disease and the risk of liver cancer.  The Cancer Cell has published the study.

Liver cancer is rising worldwide and through human studies, we’ve seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis, according to David Moore, a professor of molecular and cellular biology who led the study with Associate Professor Loning Fu, both at Baylor.  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.

Our bodies’ central circadian clock in the brain resets when we are exposed to light.  Traveling constantly through different time zones, working night shifts or pushing us to stay awake at the regular sleep time causes our central clock to be chronically disrupted.  This also extends to clocks in other tissues that are controlled by the central clock.

The researchers modeled the effects of chronic jet lag in normal mice who were fed a healthy diet by changing the times the lights went on and off during the night each week.  The mice gained weight and fat and developed fatty liver disease. This progressed to chronic inflammation and eventually to liver cancer in some of the cases.

Normal control of liver metabolism was lost on the jetlagged mice.  This included the buildup of fat and also increased production of bile acids, which are produced by the liver to help us digest our food.  Some studies linking high bile acid levels to liver cancer, in mice and humans, were done in earlier studies. Circadian clock disruption activated two nuclear receptors that help regulate liver bile acid metabolism.  A receptor called FXR, which keeps bile acid level in the liver within a normal physiological range in the jetlagged mice lacking the receptor, had higher bile acid levels and much more liver cancer. Those lacking a receptor called CAR, which regulates bile acid breakdown and known to promote liver cancer, did not get any liver tumors.

These receptors work in a similar manner in humans. The scientists did not directly study jetlag in humans, but there is evidence that sleep disruption increases both fatty liver disease and liver cancer risk in humans.

Studies show that more than 80% of the population in the U.S. adopts a lifestyle that leads to chronic disruption in their sleep schedules.  This has reached an epidemic level in other developed countries and coupled with the increase in obesity and liver cancer risk.

They hope to continue their research to further examine if drugs interacting with the nuclear receptors can help to prevent jet lag from affecting bile acid levels in the liver with a goal of using them as pharmaceutical strategies to prevent liver cancer in humans.

Bottom line results are that chronic jet lag was sufficient to induce liver cancer.  Results definitely show that chronic circadian disruption alone leads to malfunction of these receptors, so maintaining internal physiological homeostasis is very important for liver tumor suppression.

Dr Fredda Branyon

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