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Biomolecules 2015, 5(4), 2504-2537; doi:10.3390/biom5042504

The Molecular Circadian Clock and Alcohol-Induced Liver Injury

1
Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
2
Department of Psychiatry, Division of Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Natalia Osna and Kusum Kharbanda
Received: 31 July 2015 / Revised: 2 September 2015 / Accepted: 9 September 2015 / Published: 14 October 2015
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
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Abstract

Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. View Full-Text
Keywords: alcohol; ethanol; liver; hepatotoxicity; steatosis; circadian; molecular clock; circadian desynchrony alcohol; ethanol; liver; hepatotoxicity; steatosis; circadian; molecular clock; circadian desynchrony
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Udoh, U.S.; Valcin, J.A.; Gamble, K.L.; Bailey, S.M. The Molecular Circadian Clock and Alcohol-Induced Liver Injury. Biomolecules 2015, 5, 2504-2537.

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