title: n-3 fatty acids ameliorate hepatic steatosis and dysfunction after LXR agonist ingestion in mice.
abstract: Liver X receptor (LXR) agonists slow atherogenesis, but cause hepatic steatosis and dysfunction in part by increasing expression of sterol regulatory element binding protein 1-c (SREBP1-c), a transcription factor that upregulates fatty acid (FA) synthesis. n-3 FAs decrease hepatic FA synthesis by down-regulating SREBP1-c. To test the hypothesis that n-3 FAs decrease hepatic steatosis in mice given LXR agonist, C57BL/6 mice received daily gavage of an LXR agonist T0901317 (LXR(T)) or vehicle for 4weeks with concomitant intakes chow or high-fat diets enriched in saturated fat (SAT) or n-3 fat (n-3). Mice on LXR(T) and SAT developed hepatomegaly with a large increase in size and number of hepatic lipid droplets; an n-3 diet reduced liver weight/body weight with decreased hepatic steatosis and triglyceride levels. Effects of n-3 diet on hepatic lipogenesis were linked to a blunting of LXR(T) upregulation of hepatic SREBP1-c and FA synthase mRNA. n-3 diets also normalized LXR(T)-mediated increases of plasma ALT and AST levels, whereas SAT diet increased these markers.
  
  
  CONCLUSIONS
  These studies suggest that n-3 FAs when given together with LXR agonists have the potential to improve both hepatic steatosis and hepatotoxicity in humans that might receive LXR agonists to decrease risk of atherosclerosis.
authors.affiliation: Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.forename: Peri N
authors.initials: PN
authors.lastname: Millman
authors.forename: Alan R
authors.initials: AR
authors.lastname: Tall
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004041:Dietary Fats; D019587:Dietary Supplements; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D004041:Dietary Fats; D064429:Fatty Acid Synthases; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides