title: Impact of alpha-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol.
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.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Saburi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Matsubara
authors.forename: Toru
authors.initials: T
authors.lastname: Asai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: 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
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D005227:Fatty Acids; D008055:Lipids; D017392:Thiobarbituric Acid Reactive Substances; D024502:alpha-Tocopherol