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Effect of Alcohol on Clock Synchrony and Tissue Circadian Homeostasis in Mice
Luca S Santovito1, Maliha Shaikh1, Deepak Sharma1
1Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, 60612, USA.
Abstract:
Alcohol use disorder accounts for a growing worldwide health system concern. Alcohol causes damages to various organs, including intestine and liver, primarily involved in its absorption and metabolism. However, alcohol-related organ damage risk varies significantly among individuals, even when they report consuming comparable dosages of alcohol. Factor(s) that may modulate the risk of organ injuries from alcohol consumption could be responsible for inter-individual variations in susceptibility to alcohol-related organ damages. Accumulating evidence suggests disruptions in circadian rhythm can exacerbate alcohol-related organ damages. Here we investigated the interplay between alcohol, circadian rhythm, and key tissue cellular processes at baseline, after a regular and a shift in the light/dark cycle (LCD) in mice. Central/peripheral clock expression of core clock genes (CoClGs) was analyzed. We also studied circadian homeostasis of tissue cellular processes that are involved in damages from alcohol. These experiments reveal that alcohol affects the expression of CoClGs causing a central-peripheral dyssynchrony, amplified by shift in LCD. The observed circadian clock dyssynchrony was linked to circadian disorganization of key processes involved in the alcohol-related damages, particularly when alcohol was combined with LCD. These results offer insights into the mechanisms by which alcohol interacts with circadian rhythm disruption to promote organ injury.
Insights
Alcohol consumption disrupts the body's internal clock, increasing organ damage risk. This effect is worsened by changes in light/dark cycles, highlighting the link between circadian rhythm and alcohol-related injuries.
Area of Science:
- Chronobiology
- Hepatology
- Gastroenterology
Background:
- Alcohol use disorder is a significant global health issue.
- Alcohol causes organ damage, particularly in the liver and intestine.
- Individual susceptibility to alcohol-related organ damage varies.
- Circadian rhythm disruptions can worsen alcohol-induced organ injuries.
Purpose of the Study:
- To investigate the interplay between alcohol consumption, circadian rhythms, and cellular processes.
- To examine how changes in the light/dark cycle affect alcohol's impact on the circadian clock.
- To understand the mechanisms linking circadian disruption and alcohol-related organ damage.
Main Methods:
- Mice were studied at baseline and after regular and shifted light/dark cycles.
- Expression of core clock genes (CoClGs) in central and peripheral clocks was analyzed.
- Circadian homeostasis of cellular processes involved in alcohol-related damage was assessed.
Main Results:
- Alcohol consumption altered core clock gene expression, leading to central-peripheral dyssynchrony.
- Shifts in the light/dark cycle amplified this circadian dyssynchrony.
- Circadian clock dyssynchrony correlated with disorganized cellular processes crucial for alcohol metabolism and damage repair.
- The combination of alcohol and light/dark cycle shifts exacerbated these effects.
Conclusions:
- Alcohol disrupts the body's central and peripheral circadian clocks.
- Circadian rhythm disruption, especially with altered light/dark cycles, significantly exacerbates alcohol-related organ damage.
- These findings provide mechanistic insights into how alcohol and circadian disruption interact to promote organ injury.
