Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

Apr 11, 2015American journal of physiology. Gastrointestinal and liver physiology

Long-term alcohol use alters daily liver sugar storage patterns in mice

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Abstract

Chronic ethanol consumption significantly alters diurnal rhythms in hepatic glycogen metabolism.

Glycogen levels in the livers of control diet mice exhibited a robust daily rhythm, peaking during the active (dark) period.
Ethanol-fed mice showed a significant shift in glycogen peak timing to the inactive (light) period, along with decreased overall glycogen content.
Chronic ethanol intake disrupted daily patterns in the expression of several key genes and proteins involved in glycogen metabolism.
This disruption included changes in glycogen synthase, glycogenin, glucokinase, and pyruvate kinase, which are critical for glycogen synthesis and breakdown.
The findings suggest that chronic ethanol consumption may contribute to glycogen depletion and impaired energy balance in the liver.

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Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease.

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Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice

Abstract

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