Undoubtedly you have heard of the body's circadian rhythms that regulate such functions as metabolism, alertness and sleep patterns. However, physicians understand that the body has at least two circadian systems: one originating in a specific region of the brain and the other in the liver. When the balance of these systems is disturbed, their regulatory mechanisms malfunction and make metabolic disease more likely.
Liver Sets Circadian Rhythms
Although it's known that the brain, largely in response to sunlight, sends neural impulses throughout the body that regulate circadian, or daily, rhythms, research at the University of Virginia shows that the liver also sets its own circadian rhythm timed to regular meals. Furthermore, it appears that disruptions to this daily cycle can increase the risk of metabolic syndrome, diabetes, elevated cholesterol and obesity.
Writing in Liver International, Alec Davidson and co-authors found "a second circadian system that can be entrained by meal feeding" and that influences both metabolism and behavior. Although there is ample evidence of the time-keeping ability of the liver, the process is not well understood and may relate to the liver's role in preparing the body for digestion and maximum use of energy.
"These [liver] clocks are largely responsive to stimuli involved in nutrient intake," the researchers concluded.
Health Risks of Shift Workers
Shift workers are at an unusually high risk of metabolic syndrome, obesity and diabetes, not because of the nature of shift work but because of the resulting disruptions of the circadian rhythms of meals and sleep, state American and German researchers working together at the Salk Institute.
The conclusion of these studies is that eating and fasting cycles actually control the body's metabolism through the liver rather than circadian rhythms that originate in the brain, according to a paper published in the October 2009 edition of the Proceedings of the National Academy of Sciences.
"The absence of a robust circadian clock" in those whose day-night patterns are constantly changing predisposes them to metabolic diseases and dysfunctions, the researchers reported.
Sleep, Eating Patterns Important
The Salk researchers placed mice on an alternating feeding-fasting cycle and found that liver enzymes for the metabolism of sugar rise just after a meal and enzymes that break down fats rise during periods of fasting. Thus, researchers found, a regular daily feeding schedule helps the body to most efficiently burn sugar and fat.
This research addresses the link between the common American pattern of consuming snack foods throughout the day and experiencing irregular sleep patterns with metabolic disorders that arise from circadian disruptions. Not surprisingly, scientists found in this study a clear connection between distinct feeding and fasting times and optimal liver function in the metabolic process.
Diurnal Liver Enzymes and Disease
Italian researchers found that the blood levels of three liver enzymes, fibrinogen, anthithrombin III and plasmogen, fluctuate during the day in people with liver disease. They measured levels of these enzymes in five groups of 15 individuals: healthy subjects, those with alcoholic steatosis, people with chronic hepatitis, those with compensated cirrhosis and a group with uncompensated cirrhosis.
Results confirmed "the existence of a significant diurnal [daytime] periodicity in circulating levels" of the three liver enzymes, and that "rhythm derangements" of the levels of these enzymes is an accurate marker of progression in liver disease. The study did not address any cause-and-effect relationship between levels of those enzymes and liver function.
Two Circadian Systems Interact
Recent research not only confirms that the liver has its own circadian rhythm synchronized with meals, but that the interaction of this hepatic system with the circadian rhythms produced by the brain is important in the synchronization of internal physiology, especially metabolism.
More research in this area is expected to throw more light on this dual interaction of two different circadian systems, and to provide better understanding of liver "clock" mechanisms, including the metabolism of both drugs and energy.
References
- "Liver International"; Daily Oscillations in Liver Function; A.J. Davidson, Stephan F. Castanon-Cervantes; June 2004
- "Proceedings of the National Academy of Sciences"; Time of Feeding and the Intrinsic Circadian Clock Drive Rhythma in Hepatic Gene Expression; Christopher Vollmers et al.; October 2009
- "Pathophysiology of Haemostasis and Thrombosis"; Circadian Rhythms of Fibrinogen, Antithrombin III and Plasminogen in Chronic Liver Diseases of Increasing Severity; Paolo Pasqualetti et al.; 1997
