The spontaneously hypertensive rat (SHR) is a model of
cardiomyopathy that displays a genetic defect in cardiac
fatty acid (FA) translocase/CD36, a plasma membrane long-chain FA transporter.
Therapy with medium-chain FAs, which do not require CD36-facilitated transport, has been shown to improve cardiac function and
hypertrophy in SHRs despite persistent
hypertension. However, little is known about the underlying molecular mechanisms. The aim of this study was to document the impact of medium-chain
triglyceride (MCT)
therapy in SHRs on the expression level and activity of metabolic
enzymes and signaling pathways. Four-week-old male SHRs were administered MCT (SHR-MCT) or long-chain
triglyceride (SHR-LCT) for 16 wk. We used Wistar-Kyoto (WKY) rats as controls (WKY-MCT and WKY-LCT). The SHR-MCT group displayed improved cardiac dysfunction [as assessed by left ventricular (LV) end-diastolic pressure and the positive and negative first derivatives of LV pressure/P value], a shift in the
beta-myosin heavy chain (MHC)-to-alpha-MHC ratio, and
cardiac hypertrophy compared with the SHR-LCT group without an effect on blood pressure. Administration of MCT of SHRs reversed the LCT-induced reduction in the cardiac FA metabolic enzymatic activities of long-chain
3-hydroxyacyl-CoA dehydrogenase (LCHAD) and
medium-chain acyl-CoA dehydrogenase (MCAD). In the SHR-MCT group, the
protein expression and transcriptional regulation of myocardial
peroxisome proliferator-activated receptor-alpha, which regulates the transcription of LCHAD and MCAD genes, corresponded to the changes seen in those enzymatic activities. Furthermore, MCT intake caused an inhibition of JNK activation in SHR hearts. Collectively, the observed changes in the myocardial activity of metabolic
enzymes and signaling pathways may contribute to the improved cardiac dysfunction and
hypertrophy in SHRs following MCT
therapy.