Hepatocellular carcinoma (HCC) is the most common form of liver cancer. HCC was traditionally considered a rare cancer but its incidence has been steadily on the rise since the 1980’s and is now the fastest rising cause of cancer death. Major risk factors for HCC include: hepatitis infection, fungal toxin exposure (Aflatoxins), and obesity. In developed countries, nearly 50% of all HCC cases are due to fatty liver disease caused by obesity. Fatty liver disease causes accumulation of fats droplets in the liver resulting in inflammation, scaring, and liver dysfunction. It can be caused by excessive alcohol consumption (called Alcoholic Fatty liver disease) or by insulin resistance, type-2 diabetes, and obesity (called Non-alcoholic Fatty liver disease). In the developed world, Non-alcoholic Fatty liver disease is found in 95% of people who are morbidly obese. In these patients the disease can predispose them to liver cancer, specifically HCC. Another risk factor for Non-alcoholic Fatty liver disease and HCC is chronic sleep disruption as seen in people who do night-shift work. These people are also at greater risk of being obese. What we don’t know is whether disruptions in normal sleep patterns can induce Non-alcoholic Fatty liver disease and HCC in otherwise healthy people. To unravel the mechanism at play here, a group of researchers from Houston turned to mice.
The team previously has found that disruption of normal circadian rhythms in mice (disruption of sleep) can cause changes in the hormone levels in the mice that cause them to eat more food and become overweight. In this study, they disrupted the circadian rhythms and sleep of the mice and monitored markers of Non-alcoholic Fatty liver disease and HCC. They saw that 8.75% of mice who were chronically sleep deprived went on to develop HCC while none of the mice who experienced normal sleep developed HCC. Additionally, almost all mice who had chronic sleep deprivation developed Non-alcoholic Fatty liver disease in old age (96% of them) compared to the control mice in old age (only 20%). Next, the researchers impaired the function of specific proteins in the mice that are important for controlling sleep. In doing this, they were able to identify which processes in the mice were going haywire during sleep deprivation and which of these were contributing the development of Non-alcoholic Fatty liver disease and HCC. They found that two specific proteins (CAR and FXR) are key to inducing HCC in the mice. Targeting either of these two proteins may show promise in treating HCC caused by obesity and type-2 diabetes in humans.
This research provides some insight into how the sleep deprived lives of modern day society could be negatively impacting our health. It is unlikely that HCC is the only negative consequence of sleep deprivation nor the most common. The term ‘social jet lag’ describes our need to forgo sleep to connect with everything going on in our world through social media and the internet. We could all do for a little more sleep and a consistent schedule. The research presented here provides an opportunity to develop therapeutics to treat liver cancer but it also provides a good dialogue on the problems of sleep deprivation in modern society.
Image Credit: Flickr Jason Devaun