title: Liver X Receptor Agonist TO901317 Prevents Diacylglycerols Accumulation in the Heart of Streptozotocin-Diabetic Rats.
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 the heart, and enhanced LXR activity in the streptozotocin (STZ) diabetic myocardium was reported recently. The aim of this study was to investigate effect of in vivo LXR activation on myocardial lipid metabolism under conditions of STZ-induced diabetes.
  
  
  METHODS
  Wistar rats were randomly divided into three experimental groups: non-diabetic control, treated with STZ, and treated with STZ and LXR agonist - TO901317. Diabetes was induced by a single intraperitonal injection of STZ at a dose of 55 mg/kg. LXR agonist was administrated once daily in the morning by an oral gavage at a dose of 10 mg/kg/d during the last week of the experiment. After anesthesia samples of blood and the left ventricle were taken.
  
  
  RESULTS
  TO901317 administration increased expression of both LXR isoforms and its target genes: sterol response element binding protein 1c (SREBP-1c) and acetyl-coenzyme A carboxylase 1 (ACC1) in the heart of streptozotocin-diabetic rats. Treatment with LXR agonist had no effect on plasma lipids and glucose in the diabetic rats. Concomitantly, content of the examined lipid classes in the diabetic heart (nonesterified fatty acids, triacylglycerols, phospholipids, cholesterol esters, ceramide) was unchanged after treatment with TO901317. On the contrary, myocardial level of cholesterol and diacylglycerols (DAG) was decreased after LXR activation in diabetic rats, the change in DAG level was associated with downregulated expression of adipose triglyceride lipase (ATGL).
  
  
  CONCLUSIONS
  Activation of LXRs by TO901317 protects cardiomyocytes against DAG accumulation and thus may reverse disturbances in lipid metabolism observed in streptozotocin-diabetic heart.
authors.affiliation: Department of Physiology, Medical University of Biax0142;ystok, Biax0142;ystok, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Harasiuk
authors.forename: Marcin
authors.initials: M
authors.lastname: Baranowski
authors.forename: Piotr
authors.initials: P
authors.lastname: Zabielski
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.forename: Jan
authors.initials: J
authors.lastname: Górski
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D000071518:Liver X Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000103:Acetyl-CoA Carboxylase; D001786:Blood Glucose; D002784:Cholesterol; D004075:Diglycerides; D006845:Hydrocarbons, Fluorinated; D007328:Insulin; D000071518:Liver X Receptors; D047493:PPAR alpha; D047494:PPAR delta; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D014280:Triglycerides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides