Impact of alpha-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol.
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.
Takahashi
Ryotaro
R
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Okumura
Kenji
K
Matsui
Hideo
H
Saburi
Yoshihiro
Y
Kamiya
Hiroki
H
Matsubara
Kenichiro
K
Asai
Toru
T
Ito
Masafumi
M
Murohara
Toyoaki
T
D000818:Animals; D004032:Diet; D004075:Diglycerides / Q000032:analysis* / Q000737:chemistry; D004452:Echocardiography; D004734:Energy Metabolism; D005227:Fatty Acids / Q000032:analysis; D005234:Fatty Liver; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005227:Fatty Acids; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D024502:alpha-Tocopherol