Poor Sleep May Make You (and Your Liver) Fat

 

Ah, sleep. Nothing like a good dose of the stuff, right? Losing even a single wink of your usual forty (or an hour, as the case may be) is enough to throw off an entire day.
But do you know who might love sleep more than anyone or anything? Our livers.
Yes, livers. Those fleshy multivitamins with an apparent propensity for fat accumulation function best on a good night’s sleep. New research is revealing exactly why shift workers and other chronically sleep deprived members of mankind tend to have problems with obesity, insulin resistance, diabetes, heart disease, and all the other popular features of metabolic syndrome: their livers aren’t processing fat efficiently, instead allowing fat to accumulate.

Normally, teams of molecules are dispatched to the liver during the day to reduce (the totally normal) fat accumulation that occurred during the night. The teams primarily comprise two molecules, rev-erb and HDAC3, which work together to break down the liver fat. These are the day shift workers; they follow the circadian rhythm. When we don’t sleep, our circadian rhythms are disrupted. The day workers don’t show up to work at the hepatic lipid processing plant, and all the fat that accumulated during the night just sits and sits and piles up. When the workers finally return, far too much fat has built up for the teams to handle. They’re up to their neurons in it. Personally, I blame rev-erb. He’s the one with the car. He’s the one who’s supposed to drive the rest to work. HDAC3 is probably waiting on the curb, thermos and lunch pail in hand, ready to start clearing out fat, while rev-erb’s just sleeping in. Ah well – can’t really blame the workers. You have to look at the system.
Some suggest enacting a bill that removes collective bargaining rights from and reduces health benefits for hepatic lipid processing workers’ unions. I think a more prudent (and effective) approach would be to just get to bed at a reasonable time, maybe by minimizing light exposure a couple hours before sleep. For shift workers with metabolic issues who have no choice (which is, sadly, most of them) but to work those hours, the lab group is looking into whether timing the administration of drugs according to normal circadian liver metabolism would help.
All in all, this is further evidence that many (if not most) of our metabolic issues stem from liver dysfunction.
And now for something completely different. This is a totally unrelated paper but an interesting one. It presents a link between genius (IQs of 130 or greater) and prenatal exposure to higher levels of testosterone. Just as the preponderance or lack of various hormones and chemicals in utero can lead to defects or deficiencies, these researchers are proposing that the opposite can happen. Seems reasonable. But wait – before you budding parents start cycling anabolics, use a little caution. There are also links between high testosterone in the womb and autism or autism-like symptoms, and some researchers are deeming these links quite robust. I wonder if there are safe ways to fiddle with prenatal hormone exposure. Probably not.
How does a poor night’s sleep affect your metabolic health? Do you feel the acute effects right away, or do you need to get poor sleep for an extended period of time before it starts to hit you? Also, would you consider playing around with hormone levels in the womb if it meant your kid might turn out to be a genius? Let me know in the comment section!

Liver cancer rates have tripled since the 1980s. Researchers now show that persistent sleep deprivation in mice causes liver disease and eventually leads to liver cancer

Researchers have linked 'social jet lag' to increased risk of liver cancer.

The study, by a team from Baylor College of Medicine in Texas, is published in the journal Cancer Cell.
"Recent studies have shown that more than 80 percent of the population in the United States adopt a lifestyle that leads to chronic disruption in their sleep schedules," notes Loning Fu, senior author of the study and associate professor at Baylor College of Medicine.
"This has also reached an epidemic level in other developed countries, which is coupled with the increase in obesity and liver cancer risk," she adds.
"Liver cancer is on the rise worldwide, and in human studies we've now seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis," says co-lead author David Moore, professor of molecular and cellular biology.
"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," he adds.

Sleep disruption and liver cancer

The "master clock" in our brain regulates the circadian rhythms in tissues and organs around the body. This is important for sleep but also for normal metabolic function.
Shift work has already been linked to disruption of normal circadian function. A study reported by Medical News Today earlier this year, for example, linked simulated shift working patterns in mice with increased development of nonsmall cell lung cancer.
Now, researchers have associated sleep disruption with increased risk of liver cancer.
The American Cancer Society report that 700,000 people worldwide are diagnosed with liver cancer each year. Men are more likely to develop liver cancer than women. In the U.S., they estimate that over 18,000 men and nearly 9,000 women will die in 2016 from liver cancer.
Obesity is a major risk factor for hepatocellular carcinoma (HCC) - the most common type of liver cancer. Excess fat in the liver results in nonalcoholic fatty liver disease (NAFLD), which has a high incidence rate in obese individuals. NAFLD has been predicted to become the major cause of HCC in the 21st century.

Jet-lagged mice developed liver cancer, HCC

To model the effect of chronic sleep disruption - or "social jet lag," as the team describes it - mice were exposed to disrupted light and dark cycles for nearly 2 years, which resulted in prolonged disruption to their normal sleep cycles.
As a result, the mice developed a range of conditions, including skin disorders, neurodegeneration, and cancer. These were not seen in control mice, which had regular light and dark cycles. All mice received a normal diet.
Both male and female mice developed HCC by the age of 78 weeks, although, as in humans, the rates were much higher in males. Week 78 is equivalent to 67-72 years in human, which is when spontaneous development of HCC is mostly observed.
By the age of 90 weeks, 96 percent of jet-lagged mice had NAFLD, while almost 9 percent developed HCC around the same age.
Normal liver function was severely disrupted in the jet-lagged mice. Development of NAFLD was accompanied by severe inflammation and fibrosis prior to development of HCC.

Rodent gene expression patterns comparable to humans with HCC

When the researchers investigated global gene expression in the livers of jet-lagged mice, they found a pattern similar to that seen in humans with HCC.
This shows the direct effect that chronic jet lag has on gene expression, including genes involved in regulation of circadian rhythm (Bmal1, Clock, Per1, Per2 and Nr1d1), despite a lack of mutations in classic cancer genes.
Cholesterol and bile acid pathways, which are essential for normal liver function, were also disrupted. Nuclear receptor CAR, which is involved in sensing toxic compounds, was constitutively activated, while FXR, the bile acid receptor, was suppressed. This pattern is similar to HCC in humans.
"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 explains. "And thus, maintaining internal physiological homeostasis is really important for liver tumor suppression."
The team concludes that HCC caused by disruption of normal liver function could be addressed by drugs which target these receptors.

"This experiment allowed us to take several threads that were already there and put them together to come to this conclusion. We think most people would be surprised to hear that chronic jet lag was sufficient to induce liver cancer."

David Moore

Read how regular meal times could help combat jet lag.

Written by Yella Hewings-Martin