title: The Molecular Circadian Clock and Alcohol-Induced Liver Injury.
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.
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA. uduaksu@gmail.com.
authors.forename: Uduak S
authors.initials: US
authors.lastname: Udoh
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA. javalcin@uab.edu.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Valcin
authors.affiliation: Department of Psychiatry, Division of Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA. klgamble@uab.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Gamble
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA. sbailey@uab.edu.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Bailey
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000378:metabolism
chemical_list: D056950:Period Circadian Proteins; D000431:Ethanol
keywords: alcohol; circadian; circadian desynchrony; ethanol; hepatotoxicity; liver; molecular clock; steatosis