Document Detail

Peroxisome proliferator-activated receptor alpha activation induces unfavourable changes in fatty acid composition of myocardial phospholipids.
MedLine Citation:
PMID:  19617640     Owner:  NLM     Status:  MEDLINE    
Peroxisome proliferator-activated receptor alpha (PPARalpha) plays a crucial role in the transcriptional regulation of myocardial lipid metabolism. In vitro studies on isolated cardiomyocytes showed that PPARalpha activation induces expression of numerous genes involved in virtually all steps of fatty acid catabolism. However, there is very few data on the effect of PPARalpha activation on the content and composition of myocardial lipids in vivo. Therefore, our main aim was to examine effects of selective PPARalpha agonist WY-14643 on the content and fatty acid composition of major lipid classes in the heart of rats fed a standard chow (STD) or a high-fat diet (HFD). In STD rats WY-14643 paradoxically decreased palmitate oxidation rate in the heart, however, in HFD animals such effect was not observed. WY-14643 markedly reduced myocardial free fatty acid and diacylglycerol content in STD rats, whereas in HFD group the opposite effect was observed. These changes reflected alterations in plasma lipid concentration which suggests that effects of WY-14643 on the heart were indirect and secondary to changes in plasma lipid availability induced by the drug. Basal myocardial glucose uptake was not affected by PPARalpha agonist in either group, however, glycogen content in the heart was markedly increased. WY-14643 exerted profound influence on the fatty acid composition of myocardial phospholipids in both diet groups. These changes included increased percentage of monounsaturated fatty acids and replacement of n-3 polyunsaturated fatty acids (PUFA) by those from the n-6 family. This action of WY-14643 might be detrimental to the heart since n-3 PUFA possess cardioprotective and antiarrhythmic properties.
M Baranowski; A Blachnio-Zabielska; J Gorski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of physiology and pharmacology : an official journal of the Polish Physiological Society     Volume:  60     ISSN:  1899-1505     ISO Abbreviation:  J. Physiol. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-07-20     Completed Date:  2009-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9114501     Medline TA:  J Physiol Pharmacol     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  13-20     Citation Subset:  IM    
Department of Physiology, Medical University of Bialystok, Bialystok, Poland.
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MeSH Terms
Dietary Fats / administration & dosage
Diglycerides / metabolism
Fatty Acids, Nonesterified / metabolism
Fatty Acids, Omega-3 / metabolism
Lipid Metabolism / drug effects
Myocardium / metabolism*
PPAR alpha / agonists*
Phospholipids / metabolism*
Pyrimidines / adverse effects*
Rats, Wistar
Reg. No./Substance:
0/Dietary Fats; 0/Diglycerides; 0/Fatty Acids, Nonesterified; 0/Fatty Acids, Omega-3; 0/PPAR alpha; 0/Phospholipids; 0/Pyrimidines; 50892-23-4/pirinixic acid

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