Changes in distinct species of 1,2-diacylglycerol in cardiac hypertrophy due to energy metabolic disorder.

Abstract

OBJECTIVE:

The juvenile visceral steatosis (JVS) mouse, a genetic model of systemic carnitine deficiency resulting from carnitine transport mutation, develops cardiac hypertrophy. We determined two putative lipid messengers, 1,2-diacylglycerol (DAG) and ceramide, in JVS and carnitine palmitoyltransferase-I (CPT-I) inhibitor etomoxir-treated mice because these lipids function as co-messengers in the myocardium via modification of protein kinase C activity.

METHODS:

JVS mice were evaluated at 4 and 8 weeks of age. The effect of long-term etomoxir treatment (45 mg/day) (ET) on mice was investigated in control mice from 4 to 8 weeks of age. As a model of inhibited cardiac hypertrophy, carnitine-treated JVS (CT) mice were produced. Myocardial DAG and ceramide levels and their fatty acid composition were measured.

RESULTS:

The heart/body weight ratio increased by 100% in JVS mice compared with that in controls, while that of CT mice was normalized in comparison with controls at 8 weeks of age. DAG markedly increased in both JVS and ET mice compared with that in controls (1,677+/-84, 1,258+/-49, and 585+/-58 ng/dry wt, respectively; P<0.01 for controls versus JVS or ET mice), whereas it was decreased significantly in CT mice compared with that in JVS mice (1,066+/-54 ng/dry wt, P<0.01). Furthermore, the fatty acid composition of DAG was similar in JVS and ET mice; in particular, 18:1 and 18:2 were significantly elevated in the myocardium (P<0.01 versus controls). On the other hand, that of DAG in CT mice was similar to that of the control group. In contrast, no difference was observed in myocardial ceramide levels among the groups.

CONCLUSIONS:

Pharmacological intervention with etomoxir mimics changes in the lipid second messenger characteristic of genetic JVS mice. The results suggest that the increases in distinct DAG species might be involved in the pathogenesis of cardiac hypertrophy as a result of disorder of fatty acid transport.

• Authors: Yoshihiro Saburi, Kenji Okumura, Hideo Matsui, Kazunori Hayashi, Hiroki Kamiya, Ryotaro Takahashi, Kenichiro Matsubara, Masafumi Ito
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 57 Issue 1 Pg. 92-100 (Jan 2003) ISSN: 0008-6363 [Print] England
• PMID: 12504818 (Publication Type: Journal Article)

Chemical References

• 1,2-diacylglycerol
• Ceramides
• Diglycerides
• Phosphatidylcholines
• Phosphatidylinositols
• Triglycerides
• Carnitine

Topics

• Animals
• Cardiomegaly (diagnostic imaging, metabolism)
• Carnitine
• Ceramides (analysis, metabolism)
• Chromatography, Thin Layer
• Diglycerides (metabolism)
• Echocardiography
• Mice
• Mice, Inbred C3H
• Models, Animal
• Myocardium (metabolism)
• Phosphatidylcholines (analysis, metabolism)
• Phosphatidylinositols (analysis, metabolism)
• Triglycerides (analysis, metabolism)