The Molecular Circadian Clock and Alcohol-Induced Liver Injury

Biomolecules. 2015 Oct 14;5(4):2504-37. doi: 10.3390/biom5042504.

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.

Keywords: alcohol; circadian; circadian desynchrony; ethanol; hepatotoxicity; liver; molecular clock; steatosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Circadian Clocks / drug effects
  • Circadian Clocks / physiology
  • Circadian Rhythm / physiology
  • Ethanol / toxicity*
  • Humans
  • Liver / drug effects*
  • Liver / injuries
  • Liver / metabolism*
  • Period Circadian Proteins / metabolism

Substances

  • Period Circadian Proteins
  • Ethanol