The Molecular Circadian Clock and Alcohol-Induced Liver Injury

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.

The hepatic BMAL1/AKT/lipogenesis axis protects against alcoholic liver disease in mice via promoting PPARα pathway

“…Recent studies suggest a potential crosstalk between alcohol metabolism and circadian rhythms could impact the progression and severity of ALD . We observed severe liver steatosis and liver injury following ethanol feeding in two different mouse models with circadian clock deficiency in the liver, pointing to the protective role of an intact hepatic circadian clock against ALD.…”

Endocrine Adiponectin‐FGF15/19 Axis in Ethanol-Induced Inflammation and Alcoholic Liver Injury

“…Additional aberrant processes, such as circadian rhythms, 80 autophagy, 81 and ER stress 82 are associated with pathogenesis of ALD. Both adiponectin and FGF15/19 are involved in regulating circadian rhythms, 83,84 autophagy 85,86 and ER stress 87,88 .…”

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

“…Circadian clock genes also have been shown to be affect alcohol-mediated behaviors across species (Gu et al, 2009, Kovanen et al, 2010, Spanagel et al, 2005, Udoh et al, 2015). Mutations in the clock genes per1 and per2 increase alcohol intake in mice following social defeat (Dong et al, 2011, Gamsby et al, 2013, Spanagel et al, 2005).…”