LXR agonist T0901317-Induced hyperlipidemia does not lead to lipid accumulation in the rat heart.

Abstract

BACKGROUND/AIMS:

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.

CONCLUSION:

We conclude that administration of T0901317 does not lead to severe myocardial lipid accumulation in rats despite of its high plasma availability.

• Authors: Dorota Harasiuk, Marcin Baranowski, Piotr Zabielski, Adrian Chabowski, Jan Górski
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 35 Issue 3 Pg. 1095-106 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25659329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel

Chemical References

• Hydrocarbons, Fluorinated
• Liver X Receptors
• NR1H3 protein, human
• Nr1h3 protein, rat
• Orphan Nuclear Receptors
• Sulfonamides
• T0901317

Topics

• Animals
• Diet, High-Fat
• Heart Ventricles (metabolism, pathology)
• Humans
• Hydrocarbons, Fluorinated (administration & dosage)
• Hyperlipidemias (drug therapy, metabolism)
• Lipid Metabolism (drug effects)
• Liver X Receptors
• Male
• Myocardium (metabolism, pathology)
• Orphan Nuclear Receptors (agonists, biosynthesis)
• Rats
• Sulfonamides (administration & dosage)