title: Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice.
abstract: 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.
authors: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Uduak S
authors: US
authors: Udoh
authors: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Telisha M
authors: TM
authors: Swain
authors: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors: Ashley N
authors: AN
authors: Filiano
authors: Department of Psychiatry, Division of Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Karen L
authors: KL
authors: Gamble
authors: Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Martin E
authors: ME
authors: Young
authors: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama; sbailey@uab.edu.
authors: Shannon M
authors: SM
authors: Bailey
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004032:Diet; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D025001:Glycogen Phosphorylase, Liver Form; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D008112:Liver Glycogen; C051887:glycogenin; D000431:Ethanol; D005964:Glucosyltransferases; D025001:Glycogen Phosphorylase, Liver Form; D006006:Glycogen Synthase; D005941:Glucokinase
keywords: diurnal; ethanol; glycogen; glycogen synthase; liver