title: Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis.
abstract: To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis.
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Ross
authors.affiliation: Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556.
authors.forename: Cameron M
authors.initials: CM
authors.lastname: Pywell
authors.affiliation: 1] Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 [2] Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202.
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.
authors.forename: Giles E
authors.initials: GE
authors.lastname: Duffield
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005235:Fatty Liver, Alcoholic / Q000209:etiology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D009243:NAD / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D009243:NAD; D000431:Ethanol