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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Related Experiment Video

Updated: Apr 19, 2026

Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
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Circadian rhythms, alcohol and gut interactions.

Christopher B Forsyth1, Robin M Voigt2, Helen J Burgess3

  • 1Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Rush University Medical Center, Chicago, IL, USA; Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA.

Alcohol (Fayetteville, N.Y.)
|December 16, 2014
PubMed
Summary

Chronic circadian misalignment and alcohol disrupt gut barrier function, increasing alcoholic liver disease (ALD) risk. Circadian clock disruption exacerbates alcohol-induced gut leakiness and liver damage, suggesting new therapeutic targets for ALD.

Keywords:
AlcoholCircadian rhythmsCyp2e1DysbiosisIntestinal permeabilityPer2

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Area of Science:

  • * Chronobiology and Gut Health
  • * Alcoholic Liver Disease (ALD) Pathogenesis

Background:

  • * Circadian rhythms regulate numerous bodily functions, and their disruption is linked to various diseases.
  • * Chronic circadian misalignment is prevalent and increases the risk for conditions like cardiovascular disease, diabetes, cancer, and gastrointestinal disorders.
  • * Alcoholic liver disease (ALD) affects only a subset of heavy drinkers, and increased intestinal permeability ('gut leakiness') to microbial products like LPS is a key factor.

Purpose of the Study:

  • * To investigate the role of circadian clock disruption in alcohol-induced intestinal hyperpermeability and alcoholic liver disease (ALD).
  • * To explore the mechanisms by which alcohol affects circadian clock proteins (Clock and Per2) and oxidative stress in the gut.
  • * To determine if genetic or environmental disruption of circadian rhythms exacerbates alcohol-induced gut leakiness and liver pathology.

Main Methods:

  • * In vitro studies using cell cultures to examine alcohol's effects on Clock and Per2 proteins and the role of siRNA knockdown.
  • * Investigation of the involvement of intestinal Cyp2e1-mediated oxidative stress in alcohol-induced hyperpermeability.
  • * Mouse models of chronic alcohol feeding with genetic (Clock(▵19) mice) or environmental (12h phase shifting) circadian disruption.
  • * Analysis of melatonin profiles in human alcoholics to assess circadian rhythmicity.

Main Results:

  • * Alcohol increases Clock and Per2 protein levels in vitro, and their knockdown prevents alcohol-induced gut permeability.
  • * Intestinal Cyp2e1-mediated oxidative stress is essential for alcohol-induced Clock and Per2 upregulation and hyperpermeability.
  • * Circadian disruption, via genetics or environmental shifts, leads to gut leakiness and worsens alcohol-induced liver pathology in mice.
  • * Human alcoholics exhibit abnormal melatonin profiles, indicative of circadian disruption.

Conclusions:

  • * Circadian clock disruption is a significant mechanism contributing to alcohol-induced gut leakiness.
  • * Targeting circadian pathways offers a potential novel therapeutic strategy for preventing or treating alcoholic liver disease (ALD).
  • * Understanding the interplay between circadian rhythms, gut barrier function, and alcohol metabolism is crucial for ALD management.