title: Dissociation between diurnal cycles in locomotor activity, feeding behavior and hepatic PERIOD2 expression in chronic alcohol-fed mice.
abstract: Chronic alcohol consumption contributes to fatty liver disease. Our studies revealed that the hepatic circadian clock is disturbed in alcohol-induced hepatic steatosis, and effects of chronic alcohol administration upon the clock itself may contribute to steatosis. We extended these findings to explore the effects of chronic alcohol treatment on daily feeding and locomotor activity patterns. Mice were chronically pair-fed ad libitum for 4 weeks using the Lieber-DeCarli liquid diet, with calorie-controlled liquid and standard chow diets as control groups. Locomotor activity, feeding activity, and real-time bioluminescence recording of PERIOD2::LUCIFERASE expression in tissue explants were measured. Mice on liquid control and chow diets exhibited normal profiles of locomotor activity, with a ratio of 22:78% day/night activity and a peak during early night. This pattern was dramatically altered in alcohol-fed mice, marked by a 49:51% ratio and the absence of a distinct peak. While chow-diet fed mice had a normal 24:76% ratio of feeding activity, with a peak in the early night, this pattern was dramatically altered in both liquid-diet groups: mice had a 43:57% ratio, and an absence of a distinct peak. Temporal differences were also observed between the two liquid-diet groups during late day. Cosinor analysis revealed a ∼4-h and ∼6-h shift in the alcohol-fed group feeding and locomotor activity rhythms, respectively. Analysis of hepatic PER2 expression revealed that the molecular clock in alcohol-fed and control liquid-diet mice was shifted by ∼11 h and ∼6 h, respectively. No differences were observed in suprachiasmatic nucleus explants, suggesting that changes in circadian phase in the liver were generated independently from the central clock. These results suggest that chronic alcohol consumption and a liquid diet can differentially modulate the daily rhythmicity of locomotor and feeding behaviors, aspects that might contribute to disturbances in the circadian timing system and development of hepatic steatosis.
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Werner
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Sheppard
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Roudebush Veterans Administration Medical Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Suthat
authors.initials: S
authors.lastname: Liangpunsakul
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: duffield.2@nd.edu.
authors.forename: Giles E
authors.initials: GE
authors.lastname: Duffield
mesh_terms: D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D057906:Circadian Clocks / Q000187:drug effects*; D002940:Circadian Rhythm / Q000187:drug effects*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005235:Fatty Liver, Alcoholic / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D056950:Period Circadian Proteins / Q000187:drug effects* / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D000431:Ethanol
keywords: Alcoholic liver disease; Circadian rhythm; Clock gene; Feeding behavior; Hepatic steatosis; Lieber-DeCarli liquid diet