title: Obesity and Cardiac Function - The Role of Caloric Excess and its Reversal.
abstract: Obesity is recognized as an independent and increasingly prevalent risk factor for cardiovascular morbidity and mortality. This stems in part from the contribution of obesity towards insulin resistance and diabetes, which associate with premature atherosclerosis, enhanced thrombogenicity and activation of systemic inflammatory programs with resultant cardiovascular dysfunction. This review will focus on the more direct mechanisms underpinning obesity-associated cardiac pathophysiology including the metabolic consequences of lipid accumulation in the myocardium and the consequences of direct systemic effects of lipid toxicity. Furthermore, there is growing recognition that metabolic intermediates, which may be perturbed with caloric excess, may play an important role in intracellular signal transduction and on the post-translational control of metabolic functioning within the heart. As strategies to reverse obesity appear to have ameliorative cardiac effects, surgical and therapeutic approaches to facilitate weight reduction this will also be discussed.
authors.affiliation: Center for Molecular Medicine, NHLBI, NIH, Bethesda, MD.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Sack
references.citation: Endocrinology. 2003 Aug;144(8):3483-90
references.pmid: 12865329
references.citation: Circulation. 1996 Jan 1;93(1):54-9
references.pmid: 8616941
references.citation: Nat Rev Endocrinol. 2012 Apr 03;8(8):457-65
references.pmid: 22473333
references.citation: J Am Coll Cardiol. 2008 May 6;51(18):1775-83
references.pmid: 18452784
references.citation: Am J Cardiol. 1995 Dec 1;76(16):1198-201
references.pmid: 7484913
references.citation: Genes Dev. 2008 Jul 1;22(13):1753-7
references.pmid: 18550784
references.citation: N Engl J Med. 2012 Apr 26;366(17):1567-76
references.pmid: 22449319
references.citation: Biochim Biophys Acta. 2011 Jul;1813(7):1279-85
references.pmid: 21295620
references.citation: Biochim Biophys Acta. 2010 Mar;1801(3):311-9
references.pmid: 19818871
references.citation: Circulation. 2003 Aug 12;108(6):754-9
references.pmid: 12885755
references.citation: Diabetes. 2008 Nov;57(11):2933-42
references.pmid: 18716044
references.citation: Am J Physiol Heart Circ Physiol. 2012 Dec 1;303(11):H1366-73
references.pmid: 23042950
references.citation: Circ Res. 2005 May 13;96(9):939-49
references.pmid: 15890981
references.citation: Diabetes. 2007 Oct;56(10):2457-66
references.pmid: 17623815
references.citation: J Physiol. 2005 Jun 1;565(Pt 2):463-74
references.pmid: 15760936
references.citation: Mol Cell Proteomics. 2011 Dec;10(12):M111.012658
references.pmid: 21908771
references.citation: Circulation. 1965 Nov;32(5):740-5
references.pmid: 4221214
references.citation: Circulation. 2005 Oct 25;112(17):2686-95
references.pmid: 16246967
references.citation: J Am Coll Cardiol. 2006 Jan 17;47(2):398-402
references.pmid: 16412867
references.citation: Arch Intern Med. 2001 Apr 9;161(7):996-1002
references.pmid: 11295963
references.citation: Circulation. 1993 Oct;88(4 Pt 1):1431-6
references.pmid: 8403289
references.citation: Circulation. 1999 Jul 13;100(2):123-8
references.pmid: 10402440
references.citation: Nature. 2001 Dec 13;414(6865):782-7
references.pmid: 11742409
references.citation: Science. 2011 Nov 11;334(6057):806-9
references.pmid: 22076378
references.citation: Am J Med Sci. 2001 Apr;321(4):225-36
references.pmid: 11307864
references.citation: Obesity (Silver Spring). 2012 Mar;20(3):605-11
references.pmid: 21566562
references.citation: Am Heart J. 2000 Feb;139(2 Pt 1):297-304
references.pmid: 10650303
references.citation: Clin Cardiol. 2008 Nov;31(11):516-20
references.pmid: 19006115
references.citation: Biochem J. 2011 Feb 1;433(3):505-14
references.pmid: 21044047
references.citation: J Clin Endocrinol Metab. 2003 Oct;88(10):4673-6
references.pmid: 14557439
references.citation: Int J Obes Relat Metab Disord. 1999 Jan;23(1):67-74
references.pmid: 10094579
references.citation: J Clin Endocrinol Metab. 2001 Jun;86(6):2899-902
references.pmid: 11397907
references.citation: Am J Cardiol. 2005 Jun 15;95(12):1521-4
references.pmid: 15950589
references.citation: Circulation. 2003 Jun 24;107(24):3040-6
references.pmid: 12810608
references.citation: J Biol Chem. 2011 Sep 2;286(35):30561-30570
references.pmid: 21757760
references.citation: Cell Metab. 2012 Jun 6;15(6):805-12
references.pmid: 22682221
references.citation: J Lipid Res. 2006 Dec;47(12):2726-37
references.pmid: 16960261
references.citation: Circulation. 2000 Feb 29;101(8):899-907
references.pmid: 10694530
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1784-9
references.pmid: 10677535
references.citation: Cold Spring Harb Perspect Biol. 2012 Dec 01;4(12):
references.pmid: 23209156
references.citation: Am J Cardiol. 1992 Oct 1;70(9):921-4
references.pmid: 1529947
references.citation: N Engl J Med. 2007 Aug 23;357(8):741-52
references.pmid: 17715408
references.citation: Biol Chem. 2008 Mar;389(3):221-31
references.pmid: 18208353
references.citation: Surg Obes Relat Dis. 2007 Sep-Oct;3(5):503-7
references.pmid: 17903770
references.citation: Nat Rev Endocrinol. 2012 Jan 17;8(5):287-96
references.pmid: 22249520
references.citation: FASEB J. 2004 Nov;18(14):1692-700
references.pmid: 15522914
references.citation: JAMA. 2012 Feb 1;307(5):483-90
references.pmid: 22253364
references.citation: Science. 2009 May 22;324(5930):1076-80
references.pmid: 19461003
references.citation: J Am Coll Cardiol. 1997 Aug;30(2):527-32
references.pmid: 9247528
references.citation: JAMA. 2012 Feb 1;307(5):491-7
references.pmid: 22253363
references.citation: J Card Fail. 2008 Apr;14(3):198-202
references.pmid: 18381182
references.citation: Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):434-9
references.pmid: 12615693
references.citation: Science. 2010 Feb 19;327(5968):1000-4
references.pmid: 20167786
references.citation: Nat Rev Mol Cell Biol. 2012 Mar 07;13(4):270-6
references.pmid: 22395772
references.citation: Obesity (Silver Spring). 2010 Oct;18(10):1895-901
references.pmid: 20111021
references.citation: Diabetologia. 2007 Sep;50(9):1938-1948
references.pmid: 17639306
references.citation: J Mol Cell Cardiol. 2009 Jun;46(6):842-9
references.pmid: 19217910
references.citation: Circulation. 2007 Sep 4;116(10):1170-5
references.pmid: 17698735
references.citation: Am Heart J. 2001 Oct;142(4):720-4
references.pmid: 11579365
references.citation: Am J Clin Nutr. 2006 Aug;84(2):336-41
references.pmid: 16895880
references.citation: Free Radic Biol Med. 2010 Oct 15;49(7):1230-7
references.pmid: 20647045
references.citation: Circulation. 2012 Jun 12;125(23):2844-53
references.pmid: 22586279
references.citation: Circ Res. 2010 Dec 10;107(12):1470-82
references.pmid: 20947830
references.citation: Nat Med. 2011 Aug 21;17(9):1076-85
references.pmid: 21857651
references.citation: Am J Cardiol. 1995 Dec 1;76(16):1194-7
references.pmid: 7484912
references.citation: N Engl J Med. 2002 Aug 1;347(5):305-13
references.pmid: 12151467
references.citation: J Intern Med. 2001 Aug;250(2):105-20
references.pmid: 11489060
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2697-703
references.pmid: 15181044
references.citation: J Hypertens. 2008 Jul;26(7):1402-10
references.pmid: 18551017
references.citation: Am J Cardiol. 2006 Jul 1;98(1):116-20
references.pmid: 16784933
references.citation: Circ Res. 2007 May 25;100(10):1512-21
references.pmid: 17446436
references.citation: J Clin Invest. 2009 Sep;119(9):2758-71
references.pmid: 19652361
references.citation: Curr Hypertens Rep. 2012 Aug;14(4):360-5
references.pmid: 22581415
references.citation: Am J Hypertens. 2002 May;15(5):381-8
references.pmid: 12022238
references.citation: Am J Physiol Endocrinol Metab. 2000 Nov;279(5):E1104-13
references.pmid: 11052966
references.citation: Obes Res. 1999 Jul;7(4):355-62
references.pmid: 10440591
references.citation: Endocrinology. 2005 Dec;146(12):5341-9
references.pmid: 16141388
references.citation: Circulation. 2004 May 11;109(18):2191-6
references.pmid: 15123530
references.citation: Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H976-82
references.pmid: 12181126
references.citation: J Clin Invest. 2011 Jun;121(6):2111-7
references.pmid: 21633179
references.citation: N Engl J Med. 2012 Apr 26;366(17):1577-85
references.pmid: 22449317
references.citation: Obes Surg. 2001 Oct;11(5):552-8
references.pmid: 11594094
references.citation: J Clin Endocrinol Metab. 1998 Aug;83(8):2907-10
references.pmid: 9709967