Effect of Alcohol on Clock Synchrony and Tissue Circadian Homeostasis in Mice,Molecular Nutrition & Food Research

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Effect of Alcohol on Clock Synchrony and Tissue Circadian Homeostasis in Mice
Molecular Nutrition & Food Research ( IF 4.5 ) Pub Date : 2024-08-09 , DOI: 10.1002/mnfr.202400234
Luca S Santovito ₁ , Maliha Shaikh ₁ , Deepak Sharma ₁ , Christopher B Forsyth _{1,

2} , Robin M Voigt _{1,

2} , Ali Keshavarzian _{1,

2,

3} , Faraz Bishehsari _{1,

4,

5}

Affiliation

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.

中文翻译：

酒精对小鼠时钟同步和组织昼夜节律稳态的影响

酒精使用障碍是全球卫生系统日益关注的问题。酒精会对各种器官造成损害，包括肠道和肝脏，主要涉及其吸收和代谢。然而，与酒精相关的器官损伤风险在个体之间存在显着差异，即使他们报告消耗了相当剂量的酒精。可能调节饮酒引起的器官损伤风险的因素可能是造成酒精相关器官损伤易感性的个体差异的原因。越来越多的证据表明，昼夜节律的紊乱会加剧与酒精相关的器官损伤。在这里，我们研究了小鼠的光/暗周期（LCD）规律变化后，酒精、昼夜节律和关键组织细胞过程之间的相互作用。分析了核心时钟基因(CoClG)的中枢/外周时钟表达。我们还研究了与酒精损伤有关的组织细胞过程的昼夜节律稳态。这些实验表明，酒精会影响 CoClG 的表达，从而导致中枢-外周不同步，并因 LCD 的变化而放大。观察到的生物钟不同步与酒精相关损害的关键过程的昼夜节律紊乱有关，特别是当酒精与 LCD 结合时。这些结果提供了对酒精与昼夜节律破坏相互作用以促进器官损伤的机制的见解。

更新日期：2024-08-09

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