title: Dietary supplementation with docosahexaenoic acid, but not eicosapentaenoic acid, dramatically alters cardiac mitochondrial phospholipid fatty acid composition and prevents permeability transition.
abstract: Treatment with the omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exerts cardioprotective effects, and suppresses Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effects of DHA and EPA on mitochondria function. We compared the effects of dietary supplementation with the omega-3 PUFAs DHA and EPA on cardiac mitochondrial phospholipid fatty acid composition and Ca2+-induced MPTP opening. Rats were fed a standard lab diet with either normal low levels of omega-3 PUFA, or DHA or EPA at 2.5% of energy intake for 8 weeks, and cardiac mitochondria were isolated and analyzed for Ca2+-induced MPTP opening and phospholipid fatty acyl composition. DHA supplementation increased both DHA and EPA and decreased ARA in mitochondrial phospholipid, and significantly delayed MPTP opening as assessed by increased Ca2+ retention capacity and decreased Ca2+-induced mitochondria swelling. EPA supplementation increased EPA in mitochondrial phospholipids, but did not affect DHA, only modestly lowered ARA, and did not affect MPTP opening. In summary, dietary supplementation with DHA but not EPA, profoundly altered mitochondrial phospholipid fatty acid composition and delayed Ca2+-induced MPTP opening.
authors.affiliation: Division of Cardiology and Department of Medicine, University of Maryland, 20 Penn Street, HSF2, Room S022, Baltimore, MD 21201, USA.
authors.forename: Ramzi J
authors.initials: RJ
authors.lastname: Khairallah
authors.forename: Genevieve C
authors.initials: GC
authors.lastname: Sparagna
authors.forename: Nishanth
authors.initials: N
authors.lastname: Khanna
authors.forename: Karen M
authors.initials: KM
authors.lastname: O'Shea
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hecker
authors.forename: Tibor
authors.initials: T
authors.lastname: Kristian
authors.forename: Gary
authors.initials: G
authors.lastname: Fiskum
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
authors.forename: Brian M
authors.initials: BM
authors.lastname: Polster
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005227:Fatty Acids / Q000032:analysis*; D008297:Male; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D010101:Oxygen Consumption; D010743:Phospholipids / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005227:Fatty Acids; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D002118:Calcium
references.citation: Biochim Biophys Acta. 2002 Dec 30;1585(2-3):97-107
references.pmid: 12531542
references.citation: Cell Physiol Biochem. 2007;20(1-4):1-22
references.pmid: 17595511
references.citation: Cardiovasc Res. 2009 Oct 1;84(1):33-41
references.pmid: 19474179
references.citation: J Biol Chem. 2002 Sep 20;277(38):34793-9
references.pmid: 12095984
references.citation: J Mol Cell Cardiol. 2009 Dec;47(6):819-27
references.pmid: 19703463
references.citation: Biochemistry. 2000 Jun 6;39(22):6660-8
references.pmid: 10828984
references.citation: Can J Physiol Pharmacol. 1998 Jul-Aug;76(7-8):728-36
references.pmid: 10030453
references.citation: Am J Clin Nutr. 1997 Sep;66(3):649-59
references.pmid: 9280188
references.citation: Am J Physiol. 1992 Nov;263(5 Pt 2):H1479-85
references.pmid: 1332513
references.citation: Cardiovasc Res. 2009 Feb 1;81(2):319-27
references.pmid: 19015135
references.citation: Basic Res Cardiol. 2009 Mar;104(2):181-8
references.pmid: 19242640
references.citation: J Biol Chem. 2001 Oct 12;276(41):38061-7
references.pmid: 11500520
references.citation: J Lipid Res. 2008 Aug;49(8):1735-45
references.pmid: 18456640
references.citation: J Mol Cell Cardiol. 2009 Jun;46(6):850-7
references.pmid: 19233198
references.citation: J Cardiovasc Pharmacol. 2009 Apr;53(4):290-301
references.pmid: 19276988
references.citation: Biochem J. 2002 Feb 15;362(Pt 1):23-32
references.pmid: 11829736
references.citation: FASEB J. 2000 May;14(7):847-58
references.pmid: 10783138
references.citation: Nature. 2005 Mar 31;434(7033):658-62
references.pmid: 15800627
references.citation: J Mol Cell Cardiol. 2010 Feb;48(2):310-21
references.pmid: 19769982
references.citation: J Biol Chem. 2008 Sep 26;283(39):26307-11
references.pmid: 18684715
references.citation: Lancet. 2008 Oct 4;372(9645):1223-30
references.pmid: 18757090
references.citation: J Biol Chem. 2004 Jun 11;279(24):25219-25
references.pmid: 15070903
references.citation: J Biol Chem. 2001 Apr 13;276(15):12035-40
references.pmid: 11134037
references.citation: J Clin Invest. 2007 Sep;117(9):2431-44
references.pmid: 17694179
references.citation: J Mol Cell Cardiol. 2009 Jun;46(6):821-31
references.pmid: 19265700
references.citation: Biochim Biophys Acta. 2009 Nov;1787(11):1402-15
references.pmid: 19168026
references.citation: Am J Physiol. 1999 Jan;276(1):H149-58
references.pmid: 9887028
references.citation: Circ Res. 2003 Aug 22;93(4):292-301
references.pmid: 12933700
references.citation: J Pharmacol Exp Ther. 2007 May;321(2):707-15
references.pmid: 17312185
references.citation: Curr Opin Clin Nutr Metab Care. 2006 Mar;9(2):95-104
references.pmid: 16477172
references.citation: Am J Clin Nutr. 2008 Jun;87(6):1981S-90S
references.pmid: 18541599
references.citation: Circulation. 2002 May 14;105(19):2303-8
references.pmid: 12010914
references.citation: Hypertension. 2009 Sep;54(3):605-11
references.pmid: 19597033
references.citation: J Neurochem. 2000 May;74(5):1999-2009
references.pmid: 10800943
references.citation: J Lipid Res. 2005 Jun;46(6):1196-204
references.pmid: 15772420