α-生育酚对能量代谢紊乱所致心肌肥大的影响：1,2-二酰甘油的参与

Impact of alpha-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol.

作者信息

Takahashi Ryotaro, Okumura Kenji, Matsui Hideo, Saburi Yoshihiro, Kamiya Hiroki, Matsubara Kenichiro, Asai Toru, Ito Masafumi, Murohara Toyoaki

机构信息

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

出版信息

Cardiovasc Res. 2003 Jun 1;58(3):565-74. doi: 10.1016/s0008-6363(03)00291-8.

DOI:10.1016/s0008-6363(03)00291-8

PMID:12798429

Abstract

OBJECTIVE

The juvenile visceral steatosis (JVS) mouse, a murine model of systemic carnitine deficiency, shows a disorder of fatty acid oxidation and develops cardiac hypertrophy associated with lipid accumulation. Recently, alpha-tocopherol was shown to decrease 1,2-diacylglycerol (DAG) levels. We investigated the involvement of DAG in cardiac hypertrophy due to energy metabolism disorder by evaluating the effects of alpha-tocopherol administration on the hearts of JVS mice.

METHODS

Both JVS and control mice were fed a high alpha-tocopherol diet or a standard diet from 4 to 8 weeks of age. Myocardial DAG levels and fatty acid composition were assessed at 8 weeks of age.

RESULTS

The ventricular to body weight ratio in the JVS mice was significantly higher than that in the control mice [11.2+/-0.1 (mean+/-S.E.M.) versus 3.8+/-0.1 mg/g, P<0.01], and was reduced by alpha-tocopherol treatment (9.7+/-0.2 mg/g, P<0.01 versus JVS mice). However, echocardiographic analysis showed the exaggeration of left ventricular dilatation in the alpha-tocopherol treated JVS mice (P<0.01 versus JVS mice). The myocardial thiobarbituric-acid-reactive substance level was not affected by alpha-tocopherol treatment. The myocardial DAG level was 2.5-fold higher in the JVS mice compared with that in the control mice (2004+/-136 versus 806+/-36 ng/mg dry weight, P<0.01) with a significant increase in 18:1 and 18:2 fatty acids. alpha-Tocopherol treatment reduced myocardial DAG levels in the JVS mice (1443+/-49 ng/mg dry weight, P<0.01 versus JVS mice) without any alteration of the fatty acid composition.

CONCLUSIONS

alpha-Tocopherol treatment may partially reduce cardiac hypertrophy but it may also depress cardiac function in the JVS mice by decreasing the myocardial DAG level. An increase in DAG might be involved in the development of cardiac hypertrophy and in the maintenance of cardiac function in energy metabolism disorder of the heart.

摘要

目的

幼年内脏脂肪变性（JVS）小鼠是一种全身性肉碱缺乏的小鼠模型，表现出脂肪酸氧化紊乱，并出现与脂质积累相关的心脏肥大。最近，已表明α-生育酚可降低1,2 -二酰甘油（DAG）水平。我们通过评估给予α-生育酚对JVS小鼠心脏的影响，研究了DAG在能量代谢紊乱所致心脏肥大中的作用。

方法

JVS小鼠和对照小鼠在4至8周龄期间分别喂食高α-生育酚饮食或标准饮食。在8周龄时评估心肌DAG水平和脂肪酸组成。

结果

JVS小鼠的心室与体重比显著高于对照小鼠[11.2±0.1（平均值±标准误）对3.8±0.1mg/g，P<0.01]，α-生育酚治疗可使其降低（9.7±0.2mg/g，与JVS小鼠相比P<0.01）。然而，超声心动图分析显示，α-生育酚治疗的JVS小鼠左心室扩张加剧（与JVS小鼠相比P<0.01）。α-生育酚治疗对心肌硫代巴比妥酸反应性物质水平无影响。JVS小鼠的心肌DAG水平比对照小鼠高2.5倍（2004±136对806±36ng/mg干重，P<0.01），18:1和18:2脂肪酸显著增加。α-生育酚治疗降低了JVS小鼠的心肌DAG水平（1443±49ng/mg干重，与JVS小鼠相比P<0.01），且脂肪酸组成无任何改变。