Dietary medium-chain triglycerides can prevent changes in myosin and SR due to CPT-1 inhibition by etomoxir.
To define determinants of subcellular structures of heart, Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated for 5 wk with 15 mg.kg-1.day-1 etomoxir [reduces mitochondrial carnitine palmitoyltransferase-1 (CPT-1) activity and fatty acid synthesis]. To bypass CPT-1 inhibition, etomoxir-treated rats were fed a medium-chain fatty acid (MCFA) diet. Etomoxir induced a proportionate growth of heart, which could partially (WKY, P < 0.05) or completely (SHR, P < 0.05) be prevented by the MCFA diet. Also the etomoxir-induced increase in myosin V1 was partially prevented (P < 0.05). Etomoxir increased (P < 0.05) rate of sarcoplasmic reticulum (SR) Ca2+ uptake of WKY and SHR ventricular homogenates in the presence or absence of the SR Ca2+ release inhibitor ruthenium red. The MCFA diet resulted in SR Ca2+ uptake rates that were in between those of etomoxir-treated and untreated rats. The in vitro 32P incorporation into phospholamban and troponin I did not differ significantly in WKY. Etomoxir induced, however, an increase (P < 0.05) in the phosphorylated intermediate of the Ca2+ adenosinetriphosphatase in WKY that was prevented by the MCFA diet. In SHR, etomoxir increased the in vitro phospholamban phosphorylation, which was reduced compared with WKY. The data show that myosin and SR are affected by a chronically altered substrate utilization of heart.
Rupp
H
H
Molecular Cardiology, Laboratory, University of Marburg, Germany.
Schulze
W
W
Vetter
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014280:Triglycerides / Q000008:administration & dosage*; D014336:Troponin / Q000378:metabolism; D019210:Troponin I; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002334:Carnitine O-Palmitoyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases; D004041:Dietary Fats; D004852:Epoxy Compounds; D009218:Myosins; D014280:Triglycerides; D014336:Troponin; D019210:Troponin I; D000099211:Phospholamban; C054207:etomoxir