Copyright © 2005, European Society of Cardiology
Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due to systemic carnitine deficiency
aDepartment of Cardiology, Nagoya University Graduate School of Medicine,65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
bDepartment of Pathology, Nagoya University Hospital, Nagoya, Japan
* Corresponding author. Tel.: +81 52 744 2168; fax: +81 52 744 2177. Email address: kenji{at}med.nagoya-u.ac.jp
Objective: 1,2-Diacylglycerol (DAG), a lipid second messenger that activates protein kinase C (PKC), is increased with a distinct fatty acid composition in the heart of the juvenile visceral steatosis (JVS) mouse, which develops pathological cardiac hypertrophy with lipid accumulation induced by the perturbation of fatty acid β-oxidation due to systemic carnitine deficiency. Fish oil (FO) may exert its beneficial effects on the cardiomyopathy in JVS mice by modifying the molecular species composition of myocardial DAG. To test this hypothesis, we investigated the effects of dietary FO on the hypertrophied hearts in JVS mice.
Methods: Both control and JVS mice were fed a FO diet (containing 10% FO) or a standard diet from 4 weeks of age.
Results: At 8 weeks of age, the ventricular-to-body weight ratio in JVS mice was 2.7-fold higher than that in controls (9.9 ± 0.1 vs. 3.7 ± 0.1 mg/g, P<0.01) and was reduced by dietary FO (7.7 ± 0.1 mg/g, P<0.01 vs. JVS mice). In JVS mice, myocardial DAG levels were elevated by 2.3-fold with a distinct fatty acid composition with increases in C18:1n-7,9 and C18:2n-6 fatty acids compared with controls; dietary FO had no effects on the total DAG levels but significantly altered the fatty acid composition of DAG with reduction of both fatty acid species. Immunoblot analysis showed that dietary FO prevented the membrane translocation of cardiac PKCs 
, β2, and 
in JVS mice. Dietary FO did not affect the plasma and myocardial total carnitine levels in JVS mice. Furthermore, dietary FO significantly improved the progressive left ventricular dysfunction and survival rate in JVS mice.
Conclusions: Dietary FO may attenuate cardiac hypertrophy with improvements in cardiac function and survival in JVS mice via modification of the molecular species composition of myocardial DAG and the consequent inhibition of PKC redistribution. These results suggest the implication of the molecular species composition of DAG in the pathogenesis of lipotoxic cardiomyopathy due to perturbations of fatty acid β-oxidation.
KEYWORDS Cardiomyopathy; Hypertrophy; Lipid signaling; Second messengers; Protein kinase C
Time for primary review 15 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Duda, K. M. O'Shea, B. Lei, B. R. Barrows, A. M. Azimzadeh, T. E. McElfresh, B. D. Hoit, W. J. Kop, and W. C. Stanley Dietary supplementation with {omega}-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload Cardiovasc Res, November 1, 2007; 76(2): 303 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Takahashi, T. Asai, H. Murakami, R. Murakami, M. Tsuzuki, Y. Numaguchi, H. Matsui, T. Murohara, and K. Okumura Pressure Overload-Induced Cardiomyopathy in Heterozygous Carrier Mice of Carnitine Transporter Gene Mutation Hypertension, September 1, 2007; 50(3): 497 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hlavackova, J. Neckar, J. Jezkova, P. Balkova, B. Stankova, O. Novakova, F. Kolar, and F. Novak Dietary Polyunsaturated Fatty Acids Alter Myocardial Protein Kinase C Expression and Affect Cardioprotection Induced by Chronic Hypoxia Experimental Biology and Medicine, June 1, 2007; 232(6): 823 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sharma, I. C. Okere, M. K. Duda, D. J. Chess, K. M. O'Shea, and W. C. Stanley Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy Cardiovasc Res, January 15, 2007; 73(2): 257 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Asai, K. Okumura, R. Takahashi, H. Matsui, Y. Numaguchi, H. Murakami, R. Murakami, and T. Murohara Combined therapy with PPAR{alpha} agonist and L-carnitine rescues lipotoxic cardiomyopathy due to systemic carnitine deficiency Cardiovasc Res, June 1, 2006; 70(3): 566 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. Abdul Jalil, M. Horiuchi, M. Wakamatsu, M. X. Li, L. Begum, K. Suzuki, K. Kobayashi, T. Oka, and T. Saheki Attenuation of Cardiac Hypertrophy in Carnitine-Deficient Juvenile Visceral Steatosis (JVS) Mice Achieved by Lowering Dietary Lipid J. Biochem., February 1, 2006; 139(2): 263 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Stanley, F. A. Recchia, and I. C. Okere Metabolic therapies for heart disease: Fish for prevention and treatment of cardiac failure? Cardiovasc Res, November 1, 2005; 68(2): 175 - 177. [Full Text] [PDF]
|
|