Your Liver, Its Circadian Clock and Disease
The circadian clock is often associated with the brain and sleep. But did you know that your liver possesses its own clock?
A new study reveals links between alcoholic liver disease and its circadian clock…
You don’t have to drink alcohol to develop fatty liver disease. It is linked to disrupted control of fat metabolism. Is there a role of the liver’s circadian clock in the development of alcohol-induced hepatic steatosis, or fatty liver disease? Researchers at University of Notre Dame and the Indiana University School of Medicine seem to think so.
Alcohol-induced liver steatosis is produced mainly by excessive alcohol consumption and is linked to hepatitis, or inflammation of the liver. It can liver cirrhosis, intense scarring, that can lead to death. Ten percent to 35 percent of chronic heavy drinkers develop alcoholic hepatitis, and it is the main cause of liver disease in Western countries.
The team, led by associate professors Giles Duffield and Eck Institute, is interested in the molecular genetic basis for the molecular clock and this liver disease.
The study, using molecular biological approaches and long-term alcohol feeding of experimental mice (poor mice), reveals that the development of liver steatosis produced by alcohol abuse is intertwined with disturbances of the normal operation of the 24-hour clock system located in the cells of the liver.
Importantly, this change in the liver clock seems to occur independently from the master clock system located in the brain.
The circadian clock regulates 24-hour rhythms in biochemistry, physiology and behavior, and its normal operation and an important synchronization to the external world, especially the alternating cycle of day and night, is critical to maintaining a normal healthy state.
Did you know that disturbances of the clock have been linked to mental health disorders, metabolic diseases including obesity, cancer and diabetes? That is a wonderful reason to pay attention to sleep cycles and alcohol consumption.
The liver plays many roles in the body, and includes control of metabolism, fat processing, storage and release of energy and an engine for detoxification.
Liver function changes daily in a rhythmic manner and is coordinated with cycles of feeding-fasting and to the energy demands of the body, such as activity and rest. These daily rhythms are regulated by the circadian clock within those liver cells, and disturbances to the molecular clock mechanism or poor temporal coordination of the clock with the timing of eating, or the sleep-wake and rest-activity cycle, can lead to illness.
But which came first – the chicken or the egg?
Is the liver’s clock important in the actual development of the liver disease or does the development of steatosis disrupt the normal clock pattern? The researchers wonder about manipulating it for further researcher, and probably the development of drugs for treatment.
They also believe that the way chronic alcohol consumption alters liver fat metabolism shares a signal to the clock mechanism: “this being the ratio of production of reduced nicotinamide adenine dinucleotide, or NADH, to NAD+.” They think this might be the key to the shared disturbances of fat metabolism and the circadian clock.
The study, Zhou et al., was published this week in the journal Nature: Scientific Reports.