Researchers from the University of Notre Dame and the Indiana University School of Medicine have revealed a putative role for the circadian clock in the liver in the development of alcohol-induced hepatic steatosis, or fatty liver disease.Hepatic steatosis is the abnormal accumulation of fats in the cells of the liver, and is linked to disturbed control of fat metabolism. Alcohol-induced liver steatosis is produced by excessive alcohol consumption and is linked to hepatitis, or inflammation of the liver. It can be a precursor to an even more serious illness, liver cirrhosis, which includes scarring of the liver. Ten percent to 35 percent of chronic heavy drinkers develop alcoholic hepatitis, and it is the main cause of liver disease in Western countries.
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), …
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 biological clock within the SCN is thought to be the pacemaker of the circadian system, since lesions to the SCN alter circadian physiology and behaviour. The SCN co-ordinates circadian rhythms via endocrine and neural pathways. These include melatonin, the renin-angiotensin system, the hypothalamic-pituitary-adrenal axis including cortisol, and the hypothalamic-pituitary-thyroid axis and adrenaline (epinephrine). Animal studies have revealed neurological connections of the SCN to the pineal gland, heart, kidneys, adrenal cortex, liver, pancreas, spleen and white and brown adipose tissue.
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