title: An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training.
abstract: OBJECTIVE
  The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training.
  
  
  METHODS
  Sprague-Dawley rats (n = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week.
  
  
  RESULTS
  The AD resulted in a large (P < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction (P < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding.
  
  
  CONCLUSIONS
  It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.
authors.affiliation: Department of Kinesiology, Université de Montréal, C.P. 6128, Succ. centre-ville, Montreal, QC H3C 3J7, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Côté
authors.forename: Emilienne Tudor
authors.initials: ET
authors.lastname: Ngo Sock
authors.forename: Émile
authors.initials: É
authors.lastname: Lévy
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lavoie
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism; D050155:Lipogenesis / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D015243:Cholesterol, VLDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D000099150:Receptor, Farnesoid X-Activated; C106092:microsomal triglyceride transfer protein; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C532838:CYP7A1 protein, rat