title: Effects of bile duct ligation and cholic acid treatment on fatty liver in two rat models of non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease, one of the most prevalent liver disorders in Western countries, is characterized by hepatic accumulation of triglycerides. Bile acids have long been known to affect triglyceride homeostasis through a not completely understood mechanism.
  
  
  OBJECTIVE
  To analyse the effects of two different manipulations of bile acid circulation on non-alcoholic fatty liver disease.
  
  
  METHODS
  Two animal models of non-alcoholic fatty liver disease were developed by either feeding rats with a choline deficient or with a high fat diet. After 4 weeks, rats were randomized to undergo either bile duct ligation, sham operation or cholic acid administration.
  
  
  RESULTS
  During cholestasis there was an increased CYP7A1 expression, the rate limiting enzyme in bile acid synthesis, and a reduction of hepatic concentration of oxysterols, ligands of the liver X receptors. Target genes of the liver X receptors, involved in fatty acid and triglyceride synthesis, were down-regulated in association with decreased hepatic triglyceride content and improvement of fatty liver. Administration of cholic acid, ligand of farnesoid X receptor, also had a beneficial effect on fatty liver in rats on choline deficient diet.
  
  
  CONCLUSIONS
  These results indicate that pharmacological approaches increasing the expression of CYP7A1 or stimulating farnesoid X receptor pathway could represent a promising treatment for non-alcoholic fatty liver disease.
authors.affiliation: Department of Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, via Giardini 1355, Modena, Italy. chiaragabbi@virgilio.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbi
authors.forename: Marco
authors.initials: M
authors.lastname: Bertolotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Anzivino
authors.forename: Daria
authors.initials: D
authors.lastname: Macchioni
authors.forename: Marina
authors.initials: M
authors.lastname: Del Puppo
authors.forename: Matteo
authors.initials: M
authors.lastname: Ricchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Carubbi
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Dante
authors.initials: D
authors.lastname: Romagnoli
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Odoardi
authors.forename: Paola
authors.initials: P
authors.lastname: Loria
authors.forename: Luisa
authors.initials: L
authors.lastname: Losi
authors.forename: Nicola
authors.initials: N
authors.lastname: Carulli
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D019826:Cholic Acid / Q000627:therapeutic use*; D003135:Common Bile Duct / Q000601:surgery*; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000473:pathology; D000071518:Liver X Receptors; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D016896:Treatment Outcome; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D015415:Biomarkers; D002790:Cholesterol 7-alpha-Hydroxylase; D019826:Cholic Acid; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C532838:CYP7A1 protein, rat