Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure either due to transgenic expression of the lipid uptake protein acyl CoA synthetase 1 (ACS1) or overexpression of the transcription factor peroxisomal proliferator–activated receptor (PPAR) γ via the cardiac-specific myosin heavy chain (MHC) promoter. ACS1 mice and control littermates were fed 3 diets containing low-dose or high-dose FO or nonpurified diet (NPD) for 6 weeks. MHC-PPARγ mice were fed low-dose FO or NPD. Compared with control mice fed with NPD, ACS1, and MHC-PPARγ, mice fed with NPD had reduced cardiac function and survival with cardiac fibrosis. In contrast, ACS1 mice fed with high-dose FO had better cardiac function, survival, and less myocardial fibrosis. FO increased eicosapentaenoic and docosahexaenoic acids and reduced saturated fatty acids in cardiac diacylglycerols. This was associated with reduced protein kinase C alpha and beta activation. In contrast, low-dose FO reduced MHC-PPARγ mice survival with no change in protein kinase C activation or cardiac function. Thus, dietary FO reverses fibrosis and improves cardiac function and survival of ACS1 mice but does not benefit all forms of lipid-mediated cardiomyopathy.
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*Division of Preventive Medicine and Nutrition; and
†Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY;
‡Department of Medicine, Yale University School of Medicine, New Haven, CT.
Reprints: Ira J. Goldberg, MD, Department of Medicine, Columbia University, 630 West 168th Street, PH10-305, New York, NY 10032 (e-mail: email@example.com).
Supported by National Institutes of Health grants HL073029 and HL45095 (I. J. Goldberg). The authors R. S. Khan was supported by postdoctoral training grant HL007343; and K. Drosatos was supported by a postdoctoral grant from the American Heart Association (#10POST4440032). GlaxoSmithKline provided research support and the Lovaza used in the diets.
The authors have no conflict of interest to disclose.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org).
Received November 09, 2012
Accepted December 18, 2012