title: LXR agonist T0901317-Induced hyperlipidemia does not lead to lipid accumulation in the rat heart.
abstract: OBJECTIVE
  Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in human and rodent cardiac tissue, however, its role in this tissue remains unclear. The aim of this study was to investigate effects of in vivo LXR activation on lipid metabolism in the rat myocardium under the conditions of low and high lipid intake.
  
  
  METHODS
  The experiments were performed on male Wistar rats fed for 5 weeks on either low fat diet (LFD) or high fat diet (HFD). Next, the animals were randomly divided into two groups receiving either LXR agonist - T0901317 (10mg/kg/d) or vehicle for the last week of the experiment. After anesthesia samples of the left ventricle and blood were taken.
  
  
  RESULTS
  It was found that LXRβ is the dominant isoform in the rat myocardium and the expression of both LXR isoforms did not change after administration of T0901317. Agonist treatment induced hyperlipidemia in low fat fed rats and this effect was amplified in high fat fed rats. LXR agonist elevated content of myocardial triacylglycerols in animals fed on LFD and content of phospholipids in animals fed on HFD. Levels of the remaining examined lipid classes (nonesterified fatty acids, diacylglycerol, free cholesterol, cholesterol esters, ceramide) was decreased or unchaged after LXR activation.
  
  
  CONCLUSIONS
  We conclude that administration of T0901317 does not lead to severe myocardial lipid accumulation in rats despite of its high plasma availability.
authors: Department of Physiology, Medical University of Białystok, Białystok, Poland.
authors: Dorota
authors: D
authors: Harasiuk
authors: Marcin
authors: M
authors: Baranowski
authors: Piotr
authors: P
authors: Zabielski
authors: Adrian
authors: A
authors: Chabowski
authors: Jan
authors: J
authors: Górski
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D000071518:Liver X Receptors; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000096:biosynthesis*; D051381:Rats; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C000605213:NR1H3 protein, human; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides