UCI-led study reveals how consuming alcohol affects the circadian rhythm of the liver leading to disease

Irvine, Calif., November 22, 2019 – Weekend binge drinking and chronic alcoholism have long been known to contribute to alcoholic liver diseases (ALD). A new study reveals how alcohol affects the liver's circadian rhythm, uncovering a potential new target for ALD treatments. 

Drinking alcohol is a widespread habit in modern society and can have serious metabolic consequences.  Recent studies have uncovered the interplay between nutrition, metabolism and circadian rhythms. But, until now, little has been done to understand the effects of alcohol consumption on circadian metabolism.

The study, titled, "Distinct Metabolic Adaptation of Liver Circadian Pathways to Acute and Chronic Patterns of Alcohol Intake," was published today in Proceedings of National Academies of Science. 

For the study, researchers used mice to analyze the effects of binge and chronic exposure to ethanol. They revealed that distinct drinking patterns elicit profoundly different effects through distinct cellular pathways, leading to differential adaptation of hepatic circadian metabolism. 

"Our results showed how drinking patterns reprogrammed circadian metabolism in the liver," said Paolo Sassone-Corsi, director of the UCI School of Medicine Center for Epigenetics and Metabolism and senior author of the study. "By understanding how the circadian process is involved in alcoholic liver disease, we can begin to target circadian therapeutics to develop better treatments."

In earlier studies, Sassone-Corsi examined how circadian clocks can be rewired by such factors as sleep deprivation, diet and exercise. He has also discovered that the circadian clock in the liver has intrinsic functions that are independent from other organs in the body, including the brain.

This study underscores the link between circadian rhythms and alcohol metabolism.  When consumed, alcohol is primarily metabolized in the liver and is a prominent risk factor for the development of ALDs which include alcoholic hepatitis, cirrhosis and liver cancer, among others.

UCI researchers involved in the study included primary investigators Jonathan Gaucher and Kenichiro Knouchi, as well as Emilie Montellier, Carolina Magdalen Greco, Selma Masri and Pierre Baldi.  Other researchers, from LMU Munich and the Leibniz Institute for Farm Animal Biology in Germany, and the Qingdao University in China, also contributed.

The work was supported by the National Cancer Institute of the US National Institutes of Health, the European Research Council, INSERM, DARPA and in part by the Pilot Project Program of NIAAA-funded Southern California Research Center for ALPD and Cirrhosis, among other funding sources.

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