title: Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome.
abstract: Polycystic ovary syndrome (PCOS) is associated with an altered plasma lipid profile and increased risk for cardiovascular diseases. We hypothesized that molecular mechanisms underlying cardiac pathology in PCOS involve changes in expression and subcellular localization of several key proteins involved in cardiac lipid transport and metabolism, such as fatty acid transporter CD36, lipin 1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1 (PGC1), and carnitine palmitoyltransferase 1 (CPT1). We used the animal model of PCOS obtained by treating female rats with dihydrotestosterone (DHT). Protein levels of CD36, lipin 1, PPARα, PGC1, and antioxidative enzymes were assessed by Western blot in different cardiac cell compartments. Cardiac triglycerides (TG) and lipid peroxidation were also measured. The content of CD36 was decreased in both the cardiac plasma membranes and intracellular pool. On the other hand, total content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast to decreased microsomal lipin 1 content. An increase in nuclear content of lipin 1 was observed together with elevation of nuclear PPARα and PGC1, and an increase in CPT1 expression. However, lipid peroxidation was reduced in the heart, without alterations in antioxidative enzymes expression and cardiac TG content. The results indicate that treatment of female rats with DHT is accompanied by a decrease of fatty acid uptake and a reduction of lipid peroxidation in the heart. The observed elevation of lipin 1, PPARα, PGC1, and CPT1 expression suggests that cardiac fatty acid metabolism is shifted toward mitochondrial beta oxidation.
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, University of Belgrade, PO Box 522, 11001, Belgrade, Republic of Serbia.
authors.forename: Snežana
authors.initials: S
authors.lastname: Tepavčević
authors.forename: Danijela Vojnović
authors.initials: DV
authors.lastname: Milutinović
authors.forename: Djuro
authors.initials: D
authors.lastname: Macut
authors.forename: Mojca
authors.initials: M
authors.lastname: Stojiljković
authors.forename: Marina
authors.initials: M
authors.lastname: Nikolić
authors.forename: Ivana
authors.initials: I
authors.lastname: Božić-Antić
authors.forename: Tijana
authors.initials: T
authors.lastname: Ćulafić
authors.forename: Jelica
authors.initials: J
authors.lastname: Bjekić-Macut
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
authors.forename: Goran
authors.initials: G
authors.lastname: Korićanac
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D005227:Fatty Acids; C530902:Lpin1 protein, rat; D009687:Nuclear Proteins; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D014280:Triglycerides; D002334:Carnitine O-Palmitoyltransferase