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

Motoyuki Iemitsu, Nobutake Shimojo, Seiji Maeda, Yoko Irukayama-Tomobe, Satoshi Sakai, Takeshi Ohkubo, Yukihisa Tanaka, Takashi Miyauchi

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 SHRMCT 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-α-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 longchain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mediumchain acyl-CoA dehydrogenase (MCAD). In the SHR-MCT group, the protein expression and transcriptional regulation of myocardial peroxisome proliferator-activated receptor-α, 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.

Original languageEnglish
Pages (from-to)H136-H144
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number1
DOIs
Publication statusPublished - 2008 Jul
Externally publishedYes

Keywords

  • C-Jun NH -terminal kinase
  • CD36
  • Myosin heavy chain
  • Peroxisome proliferator-activated receptor-α
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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