title: Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats.
abstract: A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Wendy T K
authors.initials: WT
authors.lastname: Ip
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Andrew
authors.initials: A
authors.lastname: McAlindon
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Miller
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: James R
authors.initials: JR
authors.lastname: Bell
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Claire L
authors.initials: CL
authors.lastname: Curl
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Huggins
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Kimberley M
authors.identifier: 0000-0002-8443-9365
authors.initials: KM
authors.lastname: Mellor
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Antonia J A
authors.initials: AJ
authors.lastname: Raaijmakers
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia;
authors.forename: Laura A
authors.initials: LA
authors.lastname: Bienvenu
authors.affiliation: Graduate School of Medicine, Centre for Human Applied Physiology, University of Wollongong, Wollongong, Australia; and.
authors.forename: Peter L
authors.identifier: 0000-0003-0252-8039
authors.initials: PL
authors.lastname: McLennan
authors.affiliation: Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pepe
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Parkville, Australia; lmd@unimelb.edu.au.
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D019587:Dietary Supplements; D005227:Fatty Acids / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D015151:Immunoblotting; D000067268:Isolated Heart Preparation; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D007770:L-Lactate Dehydrogenase; D002118:Calcium
keywords: cardiomyocyte; dietary polyunsaturated fatty acids; heart; ischemia-reperfusion; sex difference