PMID- 27352290
OWN - NLM
STAT- MEDLINE
DCOM- 20170210
LR  - 20220208
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 39
IP  - 1
DP  - 2016
TI  - Liver X Receptor Agonist TO901317 Prevents Diacylglycerols Accumulation in the 
      Heart of Streptozotocin-Diabetic Rats.
PG  - 350-9
LID - 10.1159/000445629 [doi]
AB  - BACKGROUND/AIMS: Liver X receptors (LXRalpha and LXRbeta) 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). CONCLUSION: 
      Activation of LXRs by TO901317 protects cardiomyocytes against DAG accumulation 
      and thus may reverse disturbances in lipid metabolism observed in 
      streptozotocin-diabetic heart.
CI  - (c) 2016 The Author(s) Published by S. Karger AG, Basel.
FAU - Harasiuk, Dorota
AU  - Harasiuk D
AD  - Department of Physiology, Medical University of Biax0142;ystok, Biax0142;ystok, 
      Poland.
FAU - Baranowski, Marcin
AU  - Baranowski M
FAU - Zabielski, Piotr
AU  - Zabielski P
FAU - Chabowski, Adrian
AU  - Chabowski A
FAU - Gorski, Jan
AU  - Gorski J
LA  - eng
PT  - Journal Article
DEP - 20160629
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Blood Glucose)
RN  - 0 (Diglycerides)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Insulin)
RN  - 0 (Liver X Receptors)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR delta)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - Acetyl-CoA Carboxylase/metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Cholesterol/blood/metabolism
MH  - Diabetes Mellitus, Experimental/blood/genetics/*metabolism
MH  - Diglycerides/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression/drug effects
MH  - Hydrocarbons, Fluorinated/*pharmacology
MH  - Insulin/blood
MH  - Lipid Metabolism/drug effects/genetics
MH  - Liver X Receptors/*agonists/genetics/metabolism
MH  - Male
MH  - Myocardium/*metabolism
MH  - PPAR alpha/genetics/metabolism
MH  - PPAR delta/genetics/metabolism
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sterol Regulatory Element Binding Protein 1/genetics/metabolism
MH  - Sulfonamides/*pharmacology
MH  - Triglycerides/blood/metabolism
EDAT- 2016/06/29 06:00
MHDA- 2017/02/12 06:00
CRDT- 2016/06/29 06:00
PHST- 2016/06/09 00:00 [accepted]
PHST- 2016/06/29 06:00 [entrez]
PHST- 2016/06/29 06:00 [pubmed]
PHST- 2017/02/12 06:00 [medline]
AID - 000445629 [pii]
AID - 10.1159/000445629 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2016;39(1):350-9. doi: 10.1159/000445629. Epub 2016 Jun 29.