title: Fish oil selectively improves heart function in a mouse model of lipid-induced cardiomyopathy.
abstract: 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.
authors.affiliation: Division of Preventive Medicine and Nutrition, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Raffay S
authors.initials: RS
authors.lastname: Khan
authors.forename: Aalap
authors.initials: A
authors.lastname: Chokshi
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Drosatos
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.forename: Shuiqing
authors.initials: S
authors.lastname: Yu
authors.forename: Collette R
authors.initials: CR
authors.lastname: Harris
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: Li-Shin
authors.initials: LS
authors.lastname: Huang
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000473:pathology; D003066:Coenzyme A Ligases / Q000235:genetics*; D005260:Female; D005355:Fibrosis; D005395:Fish Oils / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018995:Myosin Heavy Chains / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism; D015996:Survival Rate
chemical_list: D005395:Fish Oils; D047495:PPAR gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D018995:Myosin Heavy Chains; C544400:ACSL1 protein, mouse; D003066:Coenzyme A Ligases