Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, 60612, USA.
Departments of Medicine, Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, 60612, USA.
Mol Nutr Food Res. 2024 Aug;68(16):e2400234. doi: 10.1002/mnfr.202400234. Epub 2024 Aug 9.
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.
酒精使用障碍是全球日益关注的健康系统问题。酒精会损害包括肠道和肝脏在内的各种器官，而这些器官主要参与酒精的吸收和代谢。然而，即使个体报告摄入相当剂量的酒精，他们的酒精相关器官损伤风险也存在显著差异。可能调节酒精摄入导致器官损伤风险的因素可能是导致个体对酒精相关器官损伤易感性差异的原因。越来越多的证据表明，昼夜节律紊乱会加重酒精相关的器官损伤。在这里，我们研究了在基线、定期光照/黑暗循环（LCD）和光照/黑暗循环改变后，酒精、昼夜节律和小鼠关键组织细胞过程之间的相互作用。分析了核心时钟基因（CoClGs）的中央/外周时钟表达。我们还研究了涉及酒精相关损伤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 CoClGs 的表达，导致中央-外周不同步，而 LCD 的改变会加剧这种不同步。观察到的昼夜节律时钟不同步与涉及酒精相关损伤的关键过程的昼夜节律紊乱有关，尤其是当酒精与 LCD 结合时。这些结果提供了关于酒精如何与昼夜节律紊乱相互作用以促进器官损伤的机制的见解。
