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Journal of Cardiovascular Magnetic Resonance
Published in: Journal of Cardiovascular Magnetic Resonance 1/2013

Open Access 01-12-2013 | Research

Obesity reduces left ventricular strains, torsion, and synchrony in mouse models: a cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance study

Authors: Sage P Kramer, David K Powell, Christopher M Haggerty, Cassi M Binkley, Andrea C Mattingly, Lisa A Cassis, Frederick H Epstein, Brandon K Fornwalt

Published in: Journal of Cardiovascular Magnetic Resonance | Issue 1/2013

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Abstract

Background

Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV).

Methods

Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on the diet, mice were imaged with a 7 T ClinScan using a cine DENSE protocol. Three short-axis and two long-axis slices were acquired for quantification of strains, torsion and synchrony in the left ventricle.

Results

Left ventricular mass was increased by 15% (p = 0.032) with no change in volumes or ejection fraction. Subepicardial strain was lower in the obese mice with a 40% reduction in circumferential strain (p = 0.008) a 53% reduction in radial strain (p = 0.032) and a trend towards a 19% reduction in longitudinal strain (p = 0.056). By contrast, subendocardial strain was modestly reduced in the obese mice in the circumferential direction by 12% (p = 0.028), and no different in the radial (p = 0.690) or longitudinal (p = 0.602) directions. Peak torsion was reduced by 34% (p = 0.028). Synchrony of contraction was also reduced (p = 0.032) with a time delay in the septal-to-lateral direction.

Conclusions

Diet-induced obesity reduces left ventricular strains and torsion in mice. Reductions in cardiac strain are mostly limited to the subepicardium, with relative preservation of function in the subendocardium. Diet-induced obesity also leads to reduced synchrony of contraction and hypertrophy in mouse models.
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Literature
1.
Flegal KM, Carroll MD, Kit BK, Ogden CL: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012, 307: 491-7. 10.1001/jama.2012.39.CrossRefPubMed
2.
Ogden CL, Carroll MD, Kit BK, Flegal KM: Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA. 2012, 307: 483-90. 10.1001/jama.2012.40.CrossRefPubMed
3.
Flegal KM, Graubard BI, Williamson DF, Gail MH: Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005, 293: 1861-7. 10.1001/jama.293.15.1861.CrossRefPubMed
4.
Flegal KM, Graubard BI, Williamson DF, Gail MH: Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA. 2007, 298: 2028-37. 10.1001/jama.298.17.2028.CrossRefPubMed
5.
Zhang Y, Ren J: Role of cardiac steatosis and lipotoxicity in obesity cardiomyopathy. Hypertension. 2011, 57: 148-50. 10.1161/HYPERTENSIONAHA.110.164178.CrossRefPubMed
6.
Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, Orci L, Unger RH: Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000, 97: 1784-9. 10.1073/pnas.97.4.1784.PubMedCentralCrossRefPubMed
7.
Leopoldo AS, Sugizaki MM, Lima-Leopoldo AP, do Nascimento AF, Luvizotto Rde A, de Campos DH, Okoshi K, Dal Pai-Silva M, Padovani CR, Cicogna AC: Cardiac remodeling in a rat model of diet-induced obesity. Can J Cardiol. 2010, 26: 423-9. 10.1016/S0828-282X(10)70440-2.PubMedCentralCrossRefPubMed
8.
Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, Noon GP, Frazier OH, Taegtmeyer H: Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 2004, 18: 1692-700. 10.1096/fj.04-2263com.CrossRefPubMed
9.
Aasum E, Khalid AM, Gudbrandsen OA, How OJ, Berge RK, Larsen TS: Fenofibrate modulates cardiac and hepatic metabolism and increases ischemic tolerance in diet-induced obese mice. J Mol Cell Cardiol. 2008, 44: 201-9. 10.1016/j.yjmcc.2007.08.020.CrossRefPubMed
10.
Chiu HC, Kovacs A, Ford DA, Hsu FF, Garcia R, Herrero P, Saffitz JE, Schaffer JE: A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 2001, 107: 813-22. 10.1172/JCI10947.PubMedCentralCrossRefPubMed
11.
Dobrzyn P, Dobrzyn A, Miyazaki M, Ntambi JM: Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice. J Lipid Res. 2010, 51: 2202-10. 10.1194/jlr.M003780.PubMedCentralCrossRefPubMed
12.
Dong F, Li Q, Sreejayan N, Nunn JM, Ren J: Metallothionein prevents high-fat diet induced cardiac contractile dysfunction: role of peroxisome proliferator activated receptor gamma coactivator 1alpha and mitochondrial biogenesis. Diabetes. 2007, 56: 2201-12. 10.2337/db06-1596.CrossRefPubMed
13.
Lee Y, Naseem RH, Duplomb L, Park BH, Garry DJ, Richardson JA, Schaffer JE, Unger RH: Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice. Proc Natl Acad Sci U S A. 2004, 101: 13624-9. 10.1073/pnas.0405499101.PubMedCentralCrossRefPubMed
14.
Turdi S, Kandadi MR, Zhao J, Huff AF, Du M, Ren J: Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction. J Mol Cell Cardiol. 2011, 50: 712-22. 10.1016/j.yjmcc.2010.12.007.PubMedCentralCrossRefPubMed
15.
Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, Seo T, Hu Y, Lutz EP, Merkel M, et al: Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest. 2003, 111: 419-26.PubMedCentralCrossRefPubMed
16.
Zhang Y, Yuan M, Bradley KM, Dong F, Anversa P, Ren J: Insulin-like growth factor 1 alleviates high-fat diet-induced myocardial contractile dysfunction: role of insulin signaling and mitochondrial function. Hypertension. 2012, 59: 680-93. 10.1161/HYPERTENSIONAHA.111.181867.PubMedCentralCrossRefPubMed
17.
Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, Yamada KA, Brunet S, Xu H, Nerbonne JM, et al: Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res. 2005, 96: 225-33. 10.1161/01.RES.0000154079.20681.B9.CrossRefPubMed
18.
Christoffersen C, Bollano E, Lindegaard ML, Bartels ED, Goetze JP, Andersen CB, Nielsen LB: Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 2003, 144: 3483-90. 10.1210/en.2003-0242.CrossRefPubMed
19.
Mingorance C, Duluc L, Chalopin M, Simard G, Ducluzeau PH, Herrera MD, Alvarez de Sotomayor M, Andriantsitohaina R: Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity. PLoS One. 2012, 7: e34268-10.1371/journal.pone.0034268.PubMedCentralCrossRefPubMed
20.
Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, et al: The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice. Circulation. 2012, 125 (14): 1757-64. 10.1161/CIRCULATIONAHA.111.067801. S1-6PubMedCentralCrossRefPubMed
21.
Sung MM, Koonen DP, Soltys CL, Jacobs RL, Febbraio M, Dyck JR: Increased CD36 expression in middle-aged mice contributes to obesity-related cardiac hypertrophy in the absence of cardiac dysfunction. J Mol Med (Berl). 2011, 89: 459-69. 10.1007/s00109-010-0720-4.CrossRef
22.
Thakker GD, Frangogiannis NG, Bujak M, Zymek P, Gaubatz JW, Reddy AK, Taffet G, Michael LH, Entman ML, Ballantyne CM: Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol. 2006, 291: H2504-14. 10.1152/ajpheart.00322.2006.CrossRefPubMed
23.
Ussher JR, Koves TR, Jaswal JS, Zhang L, Ilkayeva O, Dyck JR, Muoio DM, Lopaschuk GD: Insulin-stimulated cardiac glucose oxidation is increased in high-fat diet-induced obese mice lacking malonyl CoA decarboxylase. Diabetes. 2009, 58: 1766-75. 10.2337/db09-0011.PubMedCentralCrossRefPubMed
24.
Yan J, Young ME, Cui L, Lopaschuk GD, Liao R, Tian R: Increased glucose uptake and oxidation in mouse hearts prevent high fatty acid oxidation but cause cardiac dysfunction in diet-induced obesity. Circulation. 2009, 119: 2818-28. 10.1161/CIRCULATIONAHA.108.832915.PubMedCentralCrossRefPubMed
25.
Cho GY, Marwick TH, Kim HS, Kim MK, Hong KS, Oh DJ: Global 2-dimensional strain as a new prognosticator in patients with heart failure. J Am Coll Cardiol. 2009, 54: 618-24. 10.1016/j.jacc.2009.04.061.CrossRefPubMed
26.
Stanton T, Leano R, Marwick TH: Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging. 2009, 2: 356-64. 10.1161/CIRCIMAGING.109.862334.CrossRefPubMed
27.
Labombarda F, Zangl E, Dugue AE, Bougle D, Pellissier A, Ribault V, Maragnes P, Milliez P, Saloux E: Alterations of left ventricular myocardial strain in obese children. Eur Heart J Cardiovasc Imaging. 2013, 14: 668-76. 10.1093/ehjci/jes238.CrossRefPubMed
28.
Wong CY, O’Moore-Sullivan T, Leano R, Byrne N, Beller E, Marwick TH: Alterations of left ventricular myocardial characteristics associated with obesity. Circulation. 2004, 110: 3081-7. 10.1161/01.CIR.0000147184.13872.0F.CrossRefPubMed
29.
Aletras AH, Ding S, Balaban RS, Wen H: DENSE: displacement encoding with stimulated echoes in cardiac functional MRI. J Magn Reson. 1999, 137: 247-52. 10.1006/jmre.1998.1676.PubMedCentralCrossRefPubMed
30.
Spottiswoode BS, Zhong X, Hess AT, Kramer CM, Meintjes EM, Mayosi BM, Epstein FH: Tracking myocardial motion from cine DENSE images using spatiotemporal phase unwrapping and temporal fitting. IEEE Trans Med Imaging. 2007, 26: 15-30.CrossRefPubMed
31.
Kim D, Gilson WD, Kramer CM, Epstein FH: Myocardial tissue tracking with two-dimensional cine displacement-encoded MR imaging: development and initial evaluation. Radiology. 2004, 230: 862-71. 10.1148/radiol.2303021213.CrossRefPubMed
32.
Vandsburger MH, French BA, Kramer CM, Zhong X, Epstein FH: Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart. Am J Physiol Heart Circ Physiol. 2012, 302: H412-9. 10.1152/ajpheart.00705.2011.PubMedCentralCrossRefPubMed
33.
Spottiswoode BS, Zhong X, Lorenz CH, Mayosi BM, Meintjes EM, Epstein FH: Motion-guided segmentation for cine DENSE MRI. Med Image Anal. 2009, 13: 105-15. 10.1016/j.media.2008.06.016.PubMedCentralCrossRefPubMed
34.
Helm RH, Leclercq C, Faris OP, Ozturk C, McVeigh E, Lardo AC, Kass DA: Cardiac dyssynchrony analysis using circumferential versus longitudinal strain: implications for assessing cardiac resynchronization. Circulation. 2005, 111: 2760-7. 10.1161/CIRCULATIONAHA.104.508457.PubMedCentralCrossRefPubMed
35.
Henson RE, Song SK, Pastorek JS, Ackerman JJ, Lorenz CH: Left ventricular torsion is equal in mice and humans. Am J Physiol Heart Circ Physiol. 2000, 278: H1117-23.PubMed
36.
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS, American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac I: Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the cardiac imaging committee of the council on clinical cardiology of the American heart association. Circulation. 2002, 105: 539-42. 10.1161/hc0402.102975.CrossRefPubMed
37.
Haggerty CM, Kramer SP, Skrinjar O, Binkley CM, Powell DK, Mattingly AC, Epstein FH, Fornwalt BK: Quantificaiton of left ventricular volumes, mass, and ejection fraction using cine displacement encoding with stimulated echoes (DENSE) MRI. J Magn Reson Imaging. 2013, in press
38.
Purushottam B, Parameswaran AC, Figueredo VM: Dyssynchrony in obese subjects without a history of cardiac disease using velocity vector imaging. J Am Soc Echocardiogr. 2011, 24: 98-106. 10.1016/j.echo.2010.10.003.CrossRefPubMed
39.
Mogelvang R, Sogaard P, Pedersen SA, Olsen NT, Marott JL, Schnohr P, Goetze JP, Jensen JS: Cardiac dysfunction assessed by echocardiographic tissue doppler imaging is an independent predictor of mortality in the general population. Circulation. 2009, 119: 2679-85. 10.1161/CIRCULATIONAHA.108.793471.CrossRefPubMed
40.
Yiannikouris F, Gupte M, Putnam K, Thatcher S, Charnigo R, Rateri DL, Daugherty A, Cassis LA: Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice. Hypertension. 2012, 60: 1524-30. 10.1161/HYPERTENSIONAHA.112.192690.PubMedCentralCrossRefPubMed
41.
Police SB, Thatcher SE, Charnigo R, Daugherty A, Cassis LA: Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol. 2009, 29: 1458-64. 10.1161/ATVBAHA.109.192658.PubMedCentralCrossRefPubMed
42.
Gupte M, Thatcher SE, Boustany-Kari CM, Shoemaker R, Yiannikouris F, Zhang X, Karounos M, Cassis LA: Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice. Arterioscler Thromb Vasc Biol. 2012, 32: 1392-9. 10.1161/ATVBAHA.112.248559.PubMedCentralCrossRefPubMed
43.
Sakuragi S, Abhayaratna K, Gravenmaker KJ, O’Reilly C, Srikusalanukul W, Budge MM, Telford RD, Abhayaratna WP: Influence of adiposity and physical activity on arterial stiffness in healthy children: the lifestyle of our kids study. Hypertension. 2009, 53: 611-6. 10.1161/HYPERTENSIONAHA.108.123364.CrossRefPubMed
44.
Hafstad AD, Lund J, Hadler-Olsen E, Hoper AC, Larsen TS, Aasum E: High- and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes. 2013, 62: 2287-94. 10.2337/db12-1580.PubMedCentralCrossRefPubMed
45.
Spragg DD, Kass DA: Pathobiology of left ventricular dyssynchrony and resynchronization. Prog Cardiovasc Dis. 2006, 49: 26-41. 10.1016/j.pcad.2006.05.001.CrossRefPubMed
46.
Prinzen FW, Hunter WC, Wyman BT, McVeigh ER: Mapping of regional myocardial strain and work during ventricular pacing: experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol. 1999, 33: 1735-42. 10.1016/S0735-1097(99)00068-6.PubMedCentralCrossRefPubMed
47.
van Oosterhout MF, Prinzen FW, Arts T, Schreuder JJ, Vanagt WY, Cleutjens JP, Reneman RS: Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall. Circulation. 1998, 98: 588-95. 10.1161/01.CIR.98.6.588.CrossRefPubMed
48.
Vernooy K, Verbeek XA, Peschar M, Prinzen FW: Relation between abnormal ventricular impulse conduction and heart failure. J Interv Cardiol. 2003, 16: 557-62. 10.1046/j.1540-8183.2003.01061.x.CrossRefPubMed
49.
Noyan-Ashraf MH, Shikatani EA, Schuiki I, Mukovozov I, Wu J, Li RK, Volchuk A, Robinson LA, Billia F, Drucker DJ, Husain M: A glucagon-like peptide-1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity. Circulation. 2013, 127: 74-85. 10.1161/CIRCULATIONAHA.112.091215.CrossRefPubMed
50.
Cazorla O, Le Guennec JY, White E: Length-tension relationships of sub-epicardial and sub-endocardial single ventricular myocytes from rat and ferret hearts. J Mol Cell Cardiol. 2000, 32: 735-44. 10.1006/jmcc.2000.1115.CrossRefPubMed
51.
Lou Q, Fedorov VV, Glukhov AV, Moazami N, Fast VG, Efimov IR: Transmural heterogeneity and remodeling of ventricular excitation-contraction coupling in human heart failure. Circulation. 2011, 123: 1881-90. 10.1161/CIRCULATIONAHA.110.989707.PubMedCentralCrossRefPubMed
52.
van der Velden J, Merkus D, de Beer V, Hamdani N, Linke WA, Boontje NM, Stienen GJ, Duncker DJ: Transmural heterogeneity of myofilament function and sarcomeric protein phosphorylation in remodeled myocardium of pigs with a recent myocardial infarction. Front Physiol. 2011, 2: 83-PubMedCentralCrossRefPubMed
53.
Relling DP, Esberg LB, Fang CX, Johnson WT, Murphy EJ, Carlson EC, Saari JT, Ren J: High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis. J Hypertens. 2006, 24: 549-61. 10.1097/01.hjh.0000203846.34314.94.CrossRefPubMed
54.
Holland DJ, Erne D, Kostner K, Leano R, Haluska BA, Marwick TH, Sharman JE: Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction. Am J Physiol Heart Circ Physiol. 2011, 301: H123-8. 10.1152/ajpheart.00102.2011.CrossRefPubMed
55.
Zhong X, Gibberman LB, Spottiswoode BS, Gilliam AD, Meyer CH, French BA, Epstein FH: Comprehensive cardiovascular magnetic resonance of myocardial mechanics in mice using three-dimensional cine DENSE. J Cardiovasc Magn Reson. 2011, 13: 83-10.1186/1532-429X-13-83.PubMedCentralCrossRefPubMed
Metadata
Title
Obesity reduces left ventricular strains, torsion, and synchrony in mouse models: a cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance study
Authors
Sage P Kramer
David K Powell
Christopher M Haggerty
Cassi M Binkley
Andrea C Mattingly
Lisa A Cassis
Frederick H Epstein
Brandon K Fornwalt
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Cardiovascular Magnetic Resonance / Issue 1/2013
Electronic ISSN: 1532-429X
DOI
https://doi.org/10.1186/1532-429X-15-109

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