Circulation. 2004;109:2191-2196
Published online before print May 3, 2004, doi: 10.1161/01.CIR.0000127959.28627.F8
Published online before print May 3, 2004, doi: 10.1161/01.CIR.0000127959.28627.F8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:2191-2196.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women
From the Department of Medicine, Divisions of Cardiology (L.R.P., A.D.W., R.J.G.) and Geriatrics and Nutritional Science (L.R.P., S.B.R., S.K., J.M., T.M.); Mallinckrodt Institute of Radiology (P.H., Z.K.-.W., C.D., R.J.G.), and the Department of Biostatistics (K.B.S.) of Washington University School of Medicine, St Louis, Mo.
Correspondence to Linda R. Peterson, MD, Washington University School of Medicine, Campus Box 8086, 660 S Euclid Ave, St Louis, MO 63110. E-mail lpeterso{at}im.wustl.edu
Received March 5, 2003; de novo received November 18, 2003; revision received January 27, 2004; accepted February 6, 2004.
Background— Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women.
Methods and Results— We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (M
O2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/MO2. BMI correlated with MO2 (r=0.58, P=0.0006), MFAUp (r=0.42, P<0.05), and efficiency (r=–0.40, P<0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r=0.55, P<0.005), MFAU (r=0.62, P<0.001), and MFAO (r=0.58, P<0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MO2 and efficiency (P=0.0005 and P<0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P<0.05, <0.005, and <0.005, respectively).
Conclusions— In young women, obesity is a significant predictor of increased MO2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.
Key Words: obesity • metabolism • insulin
Find additional patient-related information at:
This article has been cited by other articles:
 |
|
 |
|
  P. C. Schulze Myocardial lipid accumulation and lipotoxicity in heart failure J. Lipid Res., November 1, 2009; 50(11): 2137 - 2138. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Iozzo Viewpoints on the Way to the Consensus Session: Where does insulin resistance start? The adipose tissue Diabetes Care, November 1, 2009; 32(suppl_2): S168 - S173. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bugger and E. D. Abel Rodent models of diabetic cardiomyopathy Dis. Model. Mech., September 1, 2009; 2(9-10): 454 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Bengel, T. Higuchi, M. S. Javadi, and R. Lautamaki Cardiac positron emission tomography. J. Am. Coll. Cardiol., June 30, 2009; 54(1): 1 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Bengel Clinical Cardiovascular Molecular Imaging J. Nucl. Med., June 1, 2009; 50(6): 837 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Bergman, T. Tsvetkova, B. Lowes, and E. E. Wolfel Myocardial glucose and lactate metabolism during rest and atrial pacing in humans J. Physiol., May 1, 2009; 587(9): 2087 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Boardman, A. D. Hafstad, T. S. Larsen, D. L. Severson, and E. Aasum Increased O2 cost of basal metabolism and excitation-contraction coupling in hearts from type 2 diabetic mice Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1373 - H1379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Wright, J. Kim, J. Buchanan, S. Boudina, S. Sena, K. Bakirtzi, O. Ilkun, H. A. Theobald, R. C. Cooksey, K. V. Kandror, et al. Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding Cardiovasc Res, May 1, 2009; 82(2): 351 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina, H. Bugger, S. Sena, B. T. O'Neill, V. G. Zaha, O. Ilkun, J. J. Wright, P. K. Mazumder, E. Palfreyman, T. J. Tidwell, et al. Contribution of Impaired Myocardial Insulin Signaling to Mitochondrial Dysfunction and Oxidative Stress in the Heart Circulation, March 10, 2009; 119(9): 1272 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Akki and A.-M. L. Seymour Western diet impairs metabolic remodelling and contractile efficiency in cardiac hypertrophy Cardiovasc Res, February 15, 2009; 81(3): 610 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Bergman, T. Tsvetkova, B. Lowes, and E. E. Wolfel Myocardial FFA metabolism during rest and atrial pacing in humans Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E358 - E366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Palanivel, V. Vu, M. Park, X. Fang, and G. Sweeney Differential impact of adipokines derived from primary adipocytes of wild-type versus streptozotocin-induced diabetic rats on glucose and fatty acid metabolism in cardiomyocytes J. Endocrinol., December 1, 2008; 199(3): 389 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bugger, S. Boudina, X. X. Hu, J. Tuinei, V. G. Zaha, H. A. Theobald, U. J. Yun, A. P. McQueen, B. Wayment, S. E. Litwin, et al. Type 1 Diabetic Akita Mouse Hearts Are Insulin Sensitive but Manifest Structurally Abnormal Mitochondria That Remain Coupled Despite Increased Uncoupling Protein 3 Diabetes, November 1, 2008; 57(11): 2924 - 2932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-S. Park, Y. Hu, H.-L. Noh, K. Drosatos, K. Okajima, J. Buchanan, J. Tuinei, S. Homma, X.-C. Jiang, E. D. Abel, et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy J. Lipid Res., October 1, 2008; 49(10): 2101 - 2112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Kosmala, T. M. O'Moore-Sullivan, R. Plaksej, J. Kuliczkowska-Plaksej, M. Przewlocka-Kosmala, and T. H. Marwick Subclinical Impairment of Left Ventricular Function in Young Obese Women: Contributions of Polycystic Ovary Disease and Insulin Resistance J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3748 - 3754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kuznetsova, L. Herbots, T. Richart, J. D'hooge, L. Thijs, R. H. Fagard, M.-C. Herregods, and J. A. Staessen Left ventricular strain and strain rate in a general population Eur. Heart J., August 2, 2008; 29(16): 2014 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Tabbi-Anneni, J. Buchanan, R. C. Cooksey, and E. D. Abel Captopril Normalizes Insulin Signaling and Insulin-Regulated Substrate Metabolism in Obese (ob/ob) Mouse Hearts Endocrinology, August 1, 2008; 149(8): 4043 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Harmancey, C. R. Wilson, and H. Taegtmeyer Adaptation and Maladaptation of the Heart in Obesity Hypertension, August 1, 2008; 52(2): 181 - 187. [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Peterson, P. F. Soto, P. Herrero, B. S. Mohammed, M. S. Avidan, K. B. Schechtman, C. Dence, and R. J. Gropler Impact of Gender on the Myocardial Metabolic Response to Obesity. J. Am. Coll. Cardiol. Img., July 1, 2008; 1(4): 424 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Evans and Y. Niu Hypolipidaemic effects of high-dose insulin therapy Br. J. Anaesth., April 1, 2008; 100(4): 429 - 433. [Full Text] [PDF]
|
|
|
|
|
|
S. Hammer, R. W. van der Meer, H. J. Lamb, M. Schar, A. de Roos, J. W. A. Smit, and J. A. Romijn Progressive Caloric Restriction Induces Dose-Dependent Changes in Myocardial Triglyceride Content and Diastolic Function in Healthy Men J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 497 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Witteles and M. B. Fowler Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options J. Am. Coll. Cardiol., January 15, 2008; 51(2): 93 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Peterson, P. Herrero, J. McGill, K. B. Schechtman, Z. Kisrieva-Ware, D. Lesniak, and R. J. Gropler Fatty Acids and Insulin Modulate Myocardial Substrate Metabolism in Humans With Type 1 Diabetes Diabetes, January 1, 2008; 57(1): 32 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Szczepaniak, R. G. Victor, L. Orci, and R. H. Unger Forgotten but Not Gone: The Rediscovery of Fatty Heart, the Most Common Unrecognized Disease in America Circ. Res., October 12, 2007; 101(8): 759 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boudina, S. Sena, H. Theobald, X. Sheng, J. J. Wright, X. X. Hu, S. Aziz, J. I. Johnson, H. Bugger, V. G. Zaha, et al. Mitochondrial Energetics in the Heart in Obesity-Related Diabetes: Direct Evidence for Increased Uncoupled Respiration and Activation of Uncoupling Proteins Diabetes, October 1, 2007; 56(10): 2457 - 2466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Cooper, A. Whaley-Connell, J. Habibi, Y. Wei, G. Lastra, C. Manrique, S. Stas, and J. R. Sowers Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2009 - H2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Lopaschuk, C. D.L. Folmes, and W. C. Stanley Cardiac Energy Metabolism in Obesity Circ. Res., August 17, 2007; 101(4): 335 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ashrafian, M. P. Frenneaux, and L. H. Opie Metabolic Mechanisms in Heart Failure Circulation, July 24, 2007; 116(4): 434 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Z. Song Abnormal myocardial deformation properties in obese, non-hypertensive children: an ambulatory blood pressure monitoring, standard echocardiographic, and strain rate imaging study Eur. Heart J., July 1, 2007; 28(13): 1662 - 1663. [Full Text] [PDF]
|
|
|
|
|
|
G. Di Salvo, G. Pacileo, and R. Calabro Abnormal myocardial deformation properties in obese, non-hypertensive children: an ambulatory blood pressure monitoring, standard echocardiographic, and strain rate imaging study: reply Eur. Heart J., July 1, 2007; 28(13): 1663 - 1663. [Full Text] [PDF]
|
|
|
|
|
|
S. Boudina and E. D. Abel Diabetic Cardiomyopathy Revisited Circulation, June 26, 2007; 115(25): 3213 - 3223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Perseghin, G. Ntali, F. De Cobelli, G. Lattuada, A. Esposito, E. Belloni, T. Canu, F. Costantino, F. Ragogna, P. Scifo, et al. Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance Diabetes Care, June 1, 2007; 30(6): 1520 - 1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hsueh, E. D. Abel, J. L. Breslow, N. Maeda, R. C. Davis, E. A. Fisher, H. Dansky, D. A. McClain, R. McIndoe, M. K. Wassef, et al. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease Circ. Res., May 25, 2007; 100(10): 1415 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Hafstad, A. M. Khalid, O.-J. How, T. S. Larsen, and E. Aasum Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1288 - E1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Knaapen, T. Germans, J. Knuuti, W. J. Paulus, P. A. Dijkmans, C. P. Allaart, A. A. Lammertsma, and F. C. Visser Myocardial Energetics and Efficiency: Current Status of the Noninvasive Approach Circulation, February 20, 2007; 115(7): 918 - 927. [Full Text] [PDF]
|
|
|
|
|
|
C. D.L. Folmes and G. D. Lopaschuk Role of malonyl-CoA in heart disease and the hypothalamic control of obesity Cardiovasc Res, January 15, 2007; 73(2): 278 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Van den Bergh, W. Flameng, and P. Herijgers Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions Eur J Heart Fail, December 1, 2006; 8(8): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tuunanen, E. Engblom, A. Naum, K. Nagren, B. Hesse, K. E. J. Airaksinen, P. Nuutila, P. Iozzo, H. Ukkonen, L. H. Opie, et al. Free Fatty Acid Depletion Acutely Decreases Cardiac Work and Efficiency in Cardiomyopathic Heart Failure Circulation, November 14, 2006; 114(20): 2130 - 2137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kankaanpaa, H.-R. Lehto, J. P. Parkka, M. Komu, A. Viljanen, E. Ferrannini, J. Knuuti, P. Nuutila, R. Parkkola, and P. Iozzo Myocardial Triglyceride Content and Epicardial Fat Mass in Human Obesity: Relationship to Left Ventricular Function and Serum Free Fatty Acid Levels J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4689 - 4695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G Leichman, D. Aguilar, T. M King, A. Vlada, M. Reyes, and H. Taegtmeyer Association of plasma free fatty acids and left ventricular diastolic function in patients with clinically severe obesity. Am. J. Clinical Nutrition, August 1, 2006; 84(2): 336 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boudina and E. D. Abel Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology, August 1, 2006; 21: 250 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Herrero, J. Kim, T. L. Sharp, J. A. Engelbach, J. S. Lewis, R. J. Gropler, and M. J. Welch Assessment of Myocardial Blood Flow Using 15O-Water and 1-11C-Acetate in Rats with Small-Animal PET J. Nucl. Med., March 1, 2006; 47(3): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Herrero, L. R. Peterson, J. B. McGill, S. Matthew, D. Lesniak, C. Dence, and R. J. Gropler Increased Myocardial Fatty Acid Metabolism in Patients With Type 1 Diabetes Mellitus J. Am. Coll. Cardiol., February 7, 2006; 47(3): 598 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Litwin The Growing Problem of Obesity and the Heart: The Plot "Thickens" J. Am. Coll. Cardiol., February 7, 2006; 47(3): 617 - 619. [Full Text] [PDF]
|
|
|
|
|
|
C. Y. Wong, T. O'Moore-Sullivan, R. Leano, C. Hukins, C. Jenkins, and T. H. Marwick Association of Subclinical Right Ventricular Dysfunction With Obesity J. Am. Coll. Cardiol., February 7, 2006; 47(3): 611 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Buchanan, P. K. Mazumder, P. Hu, G. Chakrabarti, M. W. Roberts, U. J. Yun, R. C. Cooksey, S. E. Litwin, and E. D. Abel Reduced Cardiac Efficiency and Altered Substrate Metabolism Precedes the Onset of Hyperglycemia and Contractile Dysfunction in Two Mouse Models of Insulin Resistance and Obesity Endocrinology, December 1, 2005; 146(12): 5341 - 5349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boudina, S. Sena, B. T. O'Neill, P. Tathireddy, M. E. Young, and E. D. Abel Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity Circulation, October 25, 2005; 112(17): 2686 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-C. Norman, B. Drinkard, J. R. McDuffie, S. Ghorbani, L. B. Yanoff, and J. A. Yanovski Influence of Excess Adiposity on Exercise Fitness and Performance in Overweight Children and Adolescents Pediatrics, June 1, 2005; 115(6): e690 - e696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.-J. How, E. Aasum, S. Kunnathu, D. L. Severson, E. S. P. Myhre, and T. S. Larsen Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2979 - H2985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Chiu, A. Kovacs, R. M. Blanton, X. Han, M. Courtois, C. J. Weinheimer, K. A. Yamada, S. Brunet, H. Xu, J. M. Nerbonne, et al. Transgenic Expression of Fatty Acid Transport Protein 1 in the Heart Causes Lipotoxic Cardiomyopathy Circ. Res., February 4, 2005; 96(2): 225 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Gibbons and P. A. Araoz The year in cardiac imaging J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1937 - 1944. [Full Text] [PDF]
|
|
|
|
|
|
C. Y. Wong, T. O'Moore-Sullivan, R. Leano, N. Byrne, E. Beller, and T. H. Marwick Alterations of Left Ventricular Myocardial Characteristics Associated With Obesity Circulation, November 9, 2004; 110(19): 3081 - 3087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Mazumder, B. T. O'Neill, M. W. Roberts, J. Buchanan, U. J. Yun, R. C. Cooksey, S. Boudina, and E. D. Abel Impaired Cardiac Efficiency and Increased Fatty Acid Oxidation in Insulin-Resistant ob/ob Mouse Hearts Diabetes, September 1, 2004; 53(9): 2366 - 2374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Reasons for Obesity-Related Cardiac Dysfunction Identified Journal Watch Women's Health, June 22, 2004; 2004(622): 1 - 1. [Full Text]
|
|