Dietary supplementation with docosahexaenoic acid, but not eicosapentaenoic acid, dramatically alters cardiac mitochondrial phospholipid fatty acid composition and prevents permeability transition.
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.
Khairallah
Ramzi J
RJ
Division of Cardiology and Department of Medicine, University of Maryland, 20 Penn Street, HSF2, Room S022, Baltimore, MD 21201, USA.
Sparagna
Genevieve C
GC
Khanna
Nishanth
N
O'Shea
Karen M
KM
Hecker
Peter A
PA
Kristian
Tibor
T
Fiskum
Gary
G
Des Rosiers
Christine
C
Polster
Brian M
BM
Stanley
William C
WC
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
D005227:Fatty Acids; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D002118:Calcium
Biochim Biophys Acta. 2002 Dec 30;1585(2-3):97-107
12531542
Cell Physiol Biochem. 2007;20(1-4):1-22
17595511
Cardiovasc Res. 2009 Oct 1;84(1):33-41
19474179
J Biol Chem. 2002 Sep 20;277(38):34793-9
12095984
J Mol Cell Cardiol. 2009 Dec;47(6):819-27
19703463
Biochemistry. 2000 Jun 6;39(22):6660-8
10828984
Can J Physiol Pharmacol. 1998 Jul-Aug;76(7-8):728-36
10030453
Am J Clin Nutr. 1997 Sep;66(3):649-59
9280188
Am J Physiol. 1992 Nov;263(5 Pt 2):H1479-85
1332513
Cardiovasc Res. 2009 Feb 1;81(2):319-27
19015135
Basic Res Cardiol. 2009 Mar;104(2):181-8
19242640
J Biol Chem. 2001 Oct 12;276(41):38061-7
11500520
J Lipid Res. 2008 Aug;49(8):1735-45
18456640
J Mol Cell Cardiol. 2009 Jun;46(6):850-7
19233198
J Cardiovasc Pharmacol. 2009 Apr;53(4):290-301
19276988
Biochem J. 2002 Feb 15;362(Pt 1):23-32
11829736
FASEB J. 2000 May;14(7):847-58
10783138
Nature. 2005 Mar 31;434(7033):658-62
15800627
J Mol Cell Cardiol. 2010 Feb;48(2):310-21
19769982
J Biol Chem. 2008 Sep 26;283(39):26307-11
18684715
Lancet. 2008 Oct 4;372(9645):1223-30
18757090
J Biol Chem. 2004 Jun 11;279(24):25219-25
15070903
J Biol Chem. 2001 Apr 13;276(15):12035-40
11134037
J Clin Invest. 2007 Sep;117(9):2431-44
17694179
J Mol Cell Cardiol. 2009 Jun;46(6):821-31
19265700
Biochim Biophys Acta. 2009 Nov;1787(11):1402-15
19168026
Am J Physiol. 1999 Jan;276(1):H149-58
9887028
Circ Res. 2003 Aug 22;93(4):292-301
12933700
J Pharmacol Exp Ther. 2007 May;321(2):707-15
17312185
Curr Opin Clin Nutr Metab Care. 2006 Mar;9(2):95-104
16477172
Am J Clin Nutr. 2008 Jun;87(6):1981S-90S
18541599
Circulation. 2002 May 14;105(19):2303-8
12010914
Hypertension. 2009 Sep;54(3):605-11
19597033
J Neurochem. 2000 May;74(5):1999-2009
10800943
J Lipid Res. 2005 Jun;46(6):1196-204
15772420