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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H136    most recent 01417.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Iemitsu, M. Articles by Miyauchi, T. Search for Related Content PubMed PubMed Citation Articles by Iemitsu, M. Articles by Miyauchi, T.

The benefit of medium-chain triglyceride therapy on the cardiac function of SHRs is associated with a reversal of metabolic and signaling alterations

¹Department of Physical Education, International Pacific University, Okayama, Okayama; ²Center for Tsukuba Advanced Research Alliance, ³Institute of Clinical Medicine, and ⁴Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki; and ⁵Tsukuba Research Laboratory, NOF Corporation, Tsukuba, Ibaraki, Japan

Submitted 27 December 2006 ; accepted in final form 25 April 2008

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 β-myosin heavy chain (MHC)-to--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-, 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.

peroxisome proliferator-activated receptor-; CD36; c-Jun NH₂-terminal kinase; myosin heavy chain; spontaneously hypertensive rats