- Research article
- Open Access
- Open Peer Review
Chronic high-fat diet-induced obesity decreased survival and increased hypertrophy of rats with experimental eccentric hypertrophy from chronic aortic regurgitation
© Dhahri et al.; licensee BioMed Central Ltd. 2014
- Received: 11 July 2014
- Accepted: 17 September 2014
- Published: 24 September 2014
The composition of a diet can influence myocardial metabolism and development of left ventricular hypertrophy (LVH). The impact of a high-fat diet in chronic left ventricular volume overload (VO) causing eccentric LVH is unknown. This study examined the effects of chronic ingestion of a high-fat diet in rats with chronic VO caused by severe aortic valve regurgitation (AR) on LVH, function and on myocardial energetics and survival.
Male Wistar rats were divided in four groups: Shams on control or high-fat (HF) diet (15 rats/group) and AR rats fed with the same diets (ARC (n = 56) and ARHF (n = 32)). HF diet was started one week before AR induction and the protocol was stopped 30 weeks later.
As expected, AR caused significant LV dilation and hypertrophy and this was exacerbated in the ARHF group. Moreover, survival in the ARHF group was significantly decreased compared the ARC group. Although the sham animals on HF also developed significant obesity compared to those on control diet, this was not associated with heart hypertrophy. The HF diet in AR rats partially countered the expected shift in myocardial energy substrate preference usually observed in heart hypertrophy (from fatty acids towards glucose). Systolic function was decreased in AR rats but HF diet had no impact on this parameter. The response to HF diet of different fatty acid oxidation markers as well as the increase in glucose transporter-4 translocation to the plasma membrane compared to ARC was blunted in AR animals compared to those on control diet.
HF diet for 30 weeks decreased survival of AR rats and worsened eccentric hypertrophy without affecting systolic function. The expected adaptation of myocardial energetics to volume-overload left ventricle hypertrophy in AR animals seemed to be impaired by the high-fat diet suggesting less metabolic flexibility.
- Left Ventricular Hypertrophy
- Control Diet
- Heart Weight
- Sham Animal
- Aortic Valve Regurgitation
Bad dietary habits have been linked to the obesity epidemic in industrialized countries. High fat (HF) diets were initially incriminated for this epidemic but this hypothesis is now being challenged. The direct cardiac toxicity of dietary sugar overabundance has been documented in animal models [1–3] but the effects of HF diets on the heart are still controversial . This is probably due to the variability of the HF diets that have been studied in rodent models of heart diseases. For example, a “Western” diet (rich in both fat and carbohydrates) has been shown to cause contractile dysfunction  in Wistar rats while a high fat/low carbohydrate diet seemed less toxic for the heart even if its content in saturated fatty acids was high .
HF diets have mostly been shown to be either neutral or somewhat beneficial in rodents with LV pressure overload [7, 8]. A neutral response to a HF diet on cardiac remodeling was also observed in a rat model of ischemic heart failure . The impact of a HF diet on dilated cardiomyopathy and eccentric LVH resulting from chronic LV volume overload (VO) has never been studied.
Chronic LV-VO causes severe dilatation and eccentric hypertrophy. It is encountered mostly in patients suffering from heart valve regurgitation (mitral or aortic). Untreated regurgitation will result in severe LV dilatation and hypertrophy as well as slowly progressive systolic dysfunction and heart failure . The obesity epidemics and the western diets have reached several developing countries worldwide . It is thus important to determine if dietary habits can influence the evolution of LV VO diseases. This study was therefore designed to assess the impact of a chronic high saturated fat diet on the development of eccentric LV hypertrophy, function and survival in rats with severe and chronic LV VO from aortic valve regurgitation (AR).
Adult male Wistar rats were purchased from Charles River (Saint-Constant QC, Canada) and divided in 4 groups as follows: 1) Sham-operated animals on control diet (SC; n = 15); 2) AR control diet (ARC; n = 56), 3) Sham on High-Fat diet (Adjusted calories diet (60% calories from fat), Cat. No. TD.06414 Harlan Teklad Madison WI), (SHF; n = 12) and AR on High-Fat diet (ARHF n = 32). The animals were maintained either on the control diet (Purina Rat Chow #5012) containing 13% calories from fat, 27% from protein and 60% from carbohydrate (39.5 g/kg from starch; 4.1kCal/g) or the high-fat diet containing 60% calories from fat, 19% protein and 21% carbohydrate (34.3 g/kg from fat; 5.4 kCal/g). The fatty acid profile (% of total fat) was 37% saturated (control diet: 19%), 47% monounsaturated (control diet: 20%) and 16% polyunsaturated (control diet: 61%). The high-fat diet was started one week before surgery in both SHF and ARHF groups and continued for 30 weeks until sacrifice. A second protocol with similar groups of animals was also investigated but for a shorter period of 8 weeks (n = 10/gr.). The protocol was approved by the Université Laval’s Animal Protection Committee and followed the recommendations of the Canadian Council on Laboratory Animal Care.
Severe AR was induced by retrograde puncture of the aortic valve leaflets as previously described . A complete echocardiographic exam with a HD11XE echograph (Philips Medical Imaging, Andover, MA) was performed two weeks after AR induction and the day before sacrifice 30 weeks later. At the end of the protocol, hearts were quickly dissected and all cardiac chambers were weighed. LV was snap-frozen in liquid nitrogen and kept at −80°C for further analysis. Serum samples were kept for evaluation of lipids, glucose, insulin and adiponectin using commercial kits.
Analysis of mRNA accumulation by quantitative RT-PCR
The analysis of LV mRNA levels by quantitative RT-PCR has been described in details elsewhere .
Enzyme activity determinations
Left ventricle samples were assayed for maximal (V max) enzyme activities. Small pieces of LV (20-30 mg) were homogenized in a glass-glass homogenizer with 9 or 39 volumes of ice-cold extracting medium pH7.4 (250 mM sucrose, 10 mM Tris–HCl, 1 mM EGTA) depending on the enzyme activity assayed. Enzymatic activities were determined as previously described [14, 15].
Crude LV homogenates were separated by SDS-PAGE. Preparation of membrane, nuclear and cytosolic fractions for the analysis of Glut4 and IRS1 translocation or AMPK subcellular localization were performed using protocols described in the following articles [16, 17]. Immunoblotting was performed as described elsewhere . All primary antibodies were used at a 1:1000 dilution and were purchased from Cell Signaling Technology (Beverly, MA) or from Santa Cruz Biotechnology (Santa Cruz,CA).
Results are presented as mean ± SEM unless specified otherwise. Normality of the data was assessed by the Pearson test. Inter-group comparisons were done using two-way ANOVA and using Bonferroni post-test if necessary. Statistical significance was set at a p < 0.05. Data and statistical analysis were performed using Graph Pad Prism version 6.01 for Windows, (San Diego CA).
Clinical data and animal characteristics
Biometric and echocardiographic parameters
60.3 ± 0.64
61.4 ± 0.31
61.0 ± 0.43
61.0 ± 0.56
1163 ± 34.0
1225 ± 34.2
1823 ± 77.0a
2046 ± 69.9a, c
8.4 ± 0.14
8.5 ± 0.17
11.4 ± 0.18a
11.6 ± 0.18a
3.8 ± 0.22
3.8 ± 0.20
6.7 ± 0.17a
6.6 ± 0.22a
78.6 ± 1.81
80.1 ± 1.52
64.8 ± 1.05a
67.9 ± 1.63a
0.30 ± 0.005
0.29 ± 0.005
0.23 ± 0.005a
0.21 ± 0.005a
126 ± 4.0
130 ± 4.0
126 ± 2.3
134 ± 4.1
1.1 ± 0.12
1.1 ± 0.12
1.4 ± 0.14
1.0 ± 0.11
3.1 ± 0.46
2.9 ± 0.12
2.6 ± 0.13
3.1 ± 0.17
17.4 ± 1.53
17.3 ± 1.72
15.9 ± 1.19
15.0 ± 1.05
1.4 ± 0.25
1.1 ± 0.19
1.6 ± 0.21a
2.4 ± 0.70a
1.1 ± 0.17
2.0 ± 0.22b
0.7 ± 0.13
2.1 ± 0.22b
10.4 ± 0.76
10.4 ± 0.69
7.7 ± 0.34
10.4 ± 0.76c
Heart weight was increased in rats with AR (Figure 2C). AR animals on the HF diet had a significantly higher heart weight than those on the control diet. Sham-operated animals fed with the HF diet had a similar heart weight to SC animals. When indexed for tibial length (Figure 2D), this difference in heart weight between ARC and ARHF animals was still significant. LV weights followed the same variations as for total heart weight (Table 1). Ejection fractions in the two AR groups were similarly decreased. Relative wall thickness (an index of LV remodeling) was similarly decreased in AR rats fed or not with the HF diet (Table 1).
LV hypertrophy markers
GSK3β and FoxO inactivation by the HF diet in eccentric LVH
Obesity has been known as an independent risk factor for cardiovascular disease  but the contribution of obesity-induced comorbidities such as dyslipidemia, hypertension or type II diabetes has to be taken into account. In humans, however, “uncomplicated” isolated obesity has been shown to be linked with cardiac anomalies too [23, 24]. Dietary habits clearly play a major role in the development of obesity and its associated complications.
Divergent results have been reported in experimental models of diet-induced obesity and heart disease depending on the composition of the abnormal diet. Some studies have suggested that diet-induced obesity does not alter cardiac function [6, 25] while others reported various cardiac systolic and/or diastolic function anomalies [26–29]. Feeding animals with LV pressure overload with a HF diet had neutral effects in some studies [7, 8, 30] but adverse effects in another . A HF diet suggested some benefits in a rat myocardial ischemia model [9, 32].
In our model of LV volume overload from AR with severe eccentric LVH, the HF diet was associated with increased LVH and poorer survival. It could be argued that the increase in heart weight in ARHF could be related only to the increased body mass. However a similar increase in heart weight should have been observed in the overweight sham animals fed the HF diet. Excessive weight gain may have played a role but it clearly was not the main factor to explain the differences. It is possible that a synergy between hemodynamic overload, diet and hypertrophy which are all pro-hypertrophic factors exist but the mechanisms for the increased hypertrophy in AR rats fed with the HF diet remain unclear. We observed in the past that the Erk 1/2 and Stat3 pathways are activated in AR [14, 15, 33]. We did not observe such an activation for the Akt/mTOR pathway in the short protocols (8 weeks) but we did in longer ones (current and ). Here, the HF diet returned the activation levels both Erk and mTOR pathways to normal suggesting that they were not responsible for the increased LVH observed in ARHF. Additional LVH may be caused by the inhibition of anti-hypertrophic molecules such as GSK3β and FoxOs. We observed increased phosphorylation of these molecules in AR rats fed with the HF diet, likely leading to their inactivation. GSK3β phosphorylation impairs its inhibition in various pathways linked to hypertrophy or cardiac growth including Wnt and NFAT signaling . FoxO favors transcription of atrogin-1, an ubiquitin ligase that promotes calcineurin degradation and can prevent NFAT activation.
Many myocardial metabolic enzymes were modulated both by the state of severe LV-VO and by the diet. The activity level of HADH was increased in SHF animals but not in SC ones. The expression of the fatty acid transporters (Fat/CD36 and CPTs) were all increased in animals on the HF diet with the exception of Fat/CD36 in the ARHF group. HF diet seems to have a stimulating effect on FAO in sham animals but this effect was somewhat blunted in AR animals. We also measured the activity levels of two enzymes of the citric acid cycle. Citrate synthase levels remained relatively stable among groups but SDH activity was strongly reduced in ARC animals. A similar observation has been made previously in a pressure overload rat model . In our model the HF diet helped restore normal levels of SDH activity.
The discrepancies between the impacts of HF diet in pressure versus volume overload models are interesting and raise some questions. Our results suggest that FAO capacity is not increased in AR animals fed a HF diet. The main source of fat in our HF diet was lard and the diet was started one week before AR induction. Unlike mice in Raher et al. , our rats did not seem to develop any clear form of metabolic syndrome or overt diabetes despite an important increase in body mass. Our results are nevertheless in line with some of the observations made in their mouse pressure-overload model. We observed more LV hypertrophy in rats on the HF diet. We also found an increase in circulating leptin in our animals. Leptin has been shown to promote the hypertrophy of cardiac myocytes . A severe pro-hypertrophic stimulus suddenly imposed to a heart with preexisting elevated leptin levels could induce an excessive hypertrophic response. Therefore, the response to this pro-hypertrophic stress may have been amplified from the very start since the HF diet had been started before AR. The heart goes through a hyper-contractile phase to compensate for the acute volume overload in the first days following AR induction . The heart has to maintain its contractile capacity and to simultaneously activate the remodeling process. These two processes both require additional energy and the HF diet could have caused enough metabolic derangements to alter them. In previous studies, PO rodent models the HF diet was started at the time of surgery. This may explain why the authors did not observe any increased LV hypertrophy in their model despite similar metabolic assessments at the end of their protocol [7, 8].
The fatty acid composition of the HF diet may influence its effects on the heart. In our study, the content of saturated and monounsaturated fatty acids was in excess of 80% of total fat. A higher content in polyunsaturated fatty acids may have led to different results. It was shown that a diet rich in omega-3 polyunsaturated fatty acid and complex carbohydrates could confer a “lipo-protection” and decrease LV hypertrophy in an pressure overload mouse model [37, 38]. This observation suggests that the composition of a HF diet specifically influence the hypertrophic response of the overloaded heart. These alternate high-fat diets with a “better” fat profile will need to be tested in upcoming protocols.
In addition to perturbing myocardial FAO, we observed that glycolysis seemed altered by the HF diet. AR LVH is associated with a shift in energy preference towards glucose . We showed that Glut4 translocation to the membrane is increased in AR animals suggesting an increased glucose uptake capacity. The HF diet completely obliterated this increase thus probably impairing the expected metabolic switch. This, in addition of probably less efficient FAO in the myocardium of AR rats fed with the HF diet could lead to increased lipotoxicity and poorer survival.
The overall oxidative capacity of the AR myocardium did not seem to be negatively altered by the HF diet. It has been reported that a HF diet in healthy rats was associated with increased FAO and oxygen consumption without an increase in function and thus with a decrease in cardiac efficiency. Uncoupling was also increased in the mitochondria, maybe as a protective mechanism against reactive oxygen species (ROS) production [39, 40]. Our results suggest a similar status in our SHF animals. In AR animals, uncoupling seems less active as suggested by the return to normal UCP3 expression. This could lessen the mitochondrial capacity to inhibit ROS production.
The exact reason why survival was decreased in the AR-HF group cannot be determined with certainty. Survival in humans with AR is directly related to LV dilatation and hypertrophy which is in line with our animal findings. Larger, more hypertrophied hearts are obviously more fragile and may be prone to pro-arrhythmia and sudden death. We did not observe any clear morphological changes in the hearts of sham-operated animals fed with the HF diet even though they were clearly overweight compared to animal on the normal diet. Recently, another study on Wistar rats has shown that a HF diet caused LV hypertrophy in healthy normal animals after 15 weeks. The investigators noticed an increase in bogy weight, circulatory insulin and leptin levels as well as an increase in myocardial collagen deposition in their animals . They also observed an increase in the papillary muscle stiffness suggesting diastolic dysfunction. In a shorter study (12 weeks) using Sprague–Dawley rats, Carroll and collaborators did not report any cardiac abnormalities . Longer studies may be necessary to reveal the true effects of a HF diet in those animals.
In conclusion, a HF diet rich in saturated fatty acids is associated with increased eccentric hypertrophy and poorer survival in a model of LV volume overload from severe AR. This suggests that dietary habits and obesity may influence the evolution of volume overload cardiomyopathy and may also possibly have an impact on survival. This could be explained in part, by the activation of pro-hypertrophic signals controlled by the GSK3β and FoxOs and an improper metabolic adaptation of the myocardium. This hypothesis could be tested in humans and the impact of dietary counseling and weight management in patients with VO should be emphasized.
This work was supported by operating grants to Dr. Couet and Arsenault from the Canadian Institutes of Health Research (MOP-61818 and MOP-106479) and the Quebec Heart and Lung University Institute Foundation.
- Chess DJ, Lei B, Hoit BD, Azimzadeh AM, Stanley WC: Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload. Am J Physiol. 2007, 293: H1853-H1860.Google Scholar
- Sharma N, Okere IC, Barrows BR, Lei B, Duda MK, Yuan CL, Previs SF, Sharov VG, Azimzadeh AM, Ernsberger P, Hoit BD, Sabbah H, Stanley WC: High-sugar diets increase cardiac dysfunction and mortality in hypertension compared to low-carbohydrate or high-starch diets. J Hypertens. 2008, 26: 1402-1410. 10.1097/HJH.0b013e3283007dda.View ArticlePubMedPubMed CentralGoogle Scholar
- Sharma N, Okere IC, Duda MK, Johnson J, Yuan CL, Chandler MP, Ernsberger P, Hoit BD, Stanley WC: High fructose diet increases mortality in hypertensive rats compared to a complex carbohydrate or high fat diet. Am J Hypertens. 2007, 20: 403-409. 10.1016/j.amjhyper.2006.09.022.View ArticlePubMedGoogle Scholar
- Chess DJ, Stanley WC: Role of diet and fuel overabundance in the development and progression of heart failure. Cardiovasc Res. 2008, 79: 269-278. 10.1093/cvr/cvn074.View ArticlePubMedGoogle Scholar
- Wilson CR, Tran MK, Salazar KL, Young ME, Taegtmeyer H: Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of wistar rats. Biochem J. 2007, 406: 457-467. 10.1042/BJ20070392.View ArticlePubMedPubMed CentralGoogle Scholar
- Okere IC, Chandler MP, McElfresh TA, Rennison JH, Sharov V, Sabbah HN, Tserng KY, Hoit BD, Ernsberger P, Young ME, Stanley WC: Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin. Am J Physiol. 2006, 291: H38-H44.Google Scholar
- Chess DJ, Khairallah RJ, O'Shea KM, Xu W, Stanley WC: A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes without affecting development of heart failure with pressure overload. Am J Physiol. 2009, 297: H1585-H1593.Google Scholar
- Chess DJ, Lei B, Hoit BD, Azimzadeh AM, Stanley WC: Effects of a high saturated fat diet on cardiac hypertrophy and dysfunction in response to pressure overload. J Card Fail. 2008, 14: 82-88. 10.1016/j.cardfail.2007.09.004.View ArticlePubMedPubMed CentralGoogle Scholar
- Rennison JH, McElfresh TA, Okere IC, Vazquez EJ, Patel HV, Foster AB, Patel KK, Chen Q, Hoit BD, Tserng KY, Hassan MO, Hoppel CL, Chandler MP: High-fat diet postinfarction enhances mitochondrial function and does not exacerbate left ventricular dysfunction. Am J Physiol. 2007, 292: H1498-H1506.Google Scholar
- Bonow RO: Aortic regurgitation. Curr Treat Opt Cardiovasc Med. 2000, 2: 125-132. 10.1007/s11936-000-0005-2.View ArticleGoogle Scholar
- van Dieren S, Beulens JW, van der Schouw YT, Grobbee DE, Neal B: The global burden of diabetes and its complications: An emerging pandemic. Eur J Cardiovasc Prev Rehab. 2010, 17 (Suppl 1): S3-S8.View ArticleGoogle Scholar
- Plante E, Couet J, Gaudreau M, Dumas MP, Drolet MC, Arsenault M: Left ventricular response to sustained volume overload from chronic aortic valve regurgitation in rats. J Card Fail. 2003, 9: 128-140. 10.1054/jcaf.2003.17.View ArticlePubMedGoogle Scholar
- Champetier S, Bojmehrani A, Beaudoin J, Lachance D, Plante E, Roussel E, Couet J, Arsenault M: Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: Rationale for targeting the beta-adrenergic and renin-angiotensin systems. Am J Physiol. 2009, 296: H669-H677.Google Scholar
- Dhahri W, Couet J, Roussel E, Drolet MC, Arsenault M: Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload. Life Sci. 2013, 92: 26-34. 10.1016/j.lfs.2012.10.022.View ArticlePubMedGoogle Scholar
- Dhahri W, Roussel E, Drolet MC, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Couet J, Arsenault M: Metformin reduces left ventricular eccentric re-modeling in experimental volume overload in the rat. J Clin Exp Cardiol. 2012, 13: 8-Google Scholar
- Battiprolu PK, Lopez-Crisosto C, Wang ZV, Nemchenko A, Lavandero S, Hill JA: Diabetic cardiomyopathy and metabolic remodeling of the heart. Life Sci. 2013, 92: 609-615. 10.1016/j.lfs.2012.10.011.View ArticlePubMedGoogle Scholar
- Gu X, Bishop SP: Increased protein kinase c and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat. Circ Res. 1994, 75: 926-931. 10.1161/01.RES.75.5.926.View ArticlePubMedGoogle Scholar
- Plante E, Lachance D, Gaudreau M, Drolet MC, Roussel E, Arsenault M, Couet J: Effectiveness of beta-blockade in experimental chronic aortic regurgitation. Circulation. 2004, 110: 1477-1483. 10.1161/01.CIR.0000141733.55236.9D.View ArticlePubMedGoogle Scholar
- Sugden PH, Fuller SJ, Weiss SC, Clerk A: Glycogen synthase kinase 3 (gsk3) in the heart: A point of integration in hypertrophic signalling and a therapeutic target? A critical analysis. Br J Pharmacol. 2008, 153 (Suppl 1): S137-S153.PubMedPubMed CentralGoogle Scholar
- Ronnebaum SM, Patterson C: The foxo family in cardiac function and dysfunction. Ann Rev Physiol. 2010, 72: 81-94. 10.1146/annurev-physiol-021909-135931.View ArticleGoogle Scholar
- Bouchard-Thomassin AA, Lachance D, Drolet MC, Couet J, Arsenault M: A high-fructose diet worsens eccentric left ventricular hypertrophy in experimental volume overload. Am J Physiol. 2011, 300: H125-H134.Google Scholar
- Hubert HB, Feinleib M, McNamara PM, Castelli WP: Obesity as an independent risk factor for cardiovascular disease: A 26-year follow-up of participants in the framingham heart study. Circulation. 1983, 67: 968-977. 10.1161/01.CIR.67.5.968.View ArticlePubMedGoogle Scholar
- Iacobellis G, Ribaudo MC, Leto G, Zappaterreno A, Vecci E, Di Mario U, Leonetti F: Influence of excess fat on cardiac morphology and function: Study in uncomplicated obesity. Ob Res. 2002, 10: 767-773. 10.1038/oby.2002.104.View ArticleGoogle Scholar
- Morricone L, Malavazos AE, Coman C, Donati C, Hassan T, Caviezel F: Echocardiographic abnormalities in normotensive obese patients: Relationship with visceral fat. Obes Res. 2002, 10: 489-498. 10.1038/oby.2002.67.View ArticlePubMedGoogle Scholar
- Carroll JF, Zenebe WJ, Strange TB: Cardiovascular function in a rat model of diet-induced obesity. Hypertension. 2006, 48: 65-72. 10.1161/01.HYP.0000224147.01024.77.View ArticlePubMedGoogle Scholar
- Carroll JF, Summers RL, Dzielak DJ, Cockrell K, Montani JP, Mizelle HL: Diastolic compliance is reduced in obese rabbits. Hypertension. 1999, 33: 811-815. 10.1161/01.HYP.33.3.811.View ArticlePubMedGoogle Scholar
- 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: 423-429. 10.1016/S0828-282X(10)70440-2.View ArticlePubMedPubMed CentralGoogle Scholar
- Ouwens DM, Boer C, Fodor M, de Galan P, Heine RJ, Maassen JA, Diamant M: Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats. Diabetologia. 2005, 48: 1229-1237. 10.1007/s00125-005-1755-x.View ArticlePubMedGoogle Scholar
- 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: 549-561. 10.1097/01.hjh.0000203846.34314.94.View ArticlePubMedGoogle Scholar
- Okere IC, Chess DJ, McElfresh TA, Johnson J, Rennison J, Ernsberger P, Hoit BD, Chandler MP, Stanley WC: High-fat diet prevents cardiac hypertrophy and improves contractile function in the hypertensive dahl salt-sensitive rat. Clin Exp Pharmacol Physiol. 2005, 32: 825-831. 10.1111/j.1440-1681.2005.04272.x.View ArticlePubMedGoogle Scholar
- Raher MJ, Thibault HB, Buys ES, Kuruppu D, Shimizu N, Brownell AL, Blake SL, Rieusset J, Kaneki M, Derumeaux G, Picard MH, Bloch KD, Scherrer-Crosbie M: A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload. Am J Physiol. 2008, 295: H2495-H2502.Google Scholar
- Rennison JH, McElfresh TA, Chen X, Anand VR, Hoit BD, Hoppel CL, Chandler MP: Prolonged exposure to high dietary lipids is not associated with lipotoxicity in heart failure. J Mol Cell Cardiol. 2009, 46: 883-890. 10.1016/j.yjmcc.2009.02.019.View ArticlePubMedPubMed CentralGoogle Scholar
- Lachance D, Plante E, Roussel E, Drolet MC, Couet J, Arsenault M: Early left ventricular remodeling in acute severe aortic regurgitation: Insights from an animal model. J Heart Valve Dis. 2008, 17: 300-308.PubMedGoogle Scholar
- Arsenault M, Zendaoui A, Roussel E, Drolet MC, Dhahri W, Grenier A, Gascon S, Sarrhini O, Rousseau JA, Lecomte R, Couet J: Angiotensin II converting enzyme inhibition improves survival, ventricular remodeling and myocardial energetics in experimental aortic regurgitation. Circ Heart Fail. 2013, 6: 1021-1028. 10.1161/CIRCHEARTFAILURE.112.000045.View ArticlePubMedGoogle Scholar
- Cheng H, Woodgett J, Maamari M, Force T: Targeting gsk-3 family members in the heart: A very sharp double-edged sword. J Mol Cell Cardiol. 2011, 51: 607-613. 10.1016/j.yjmcc.2010.11.020.View ArticlePubMedGoogle Scholar
- Karmazyn M, Purdham DM, Rajapurohitam V, Zeidan A: Leptin as a cardiac hypertrophic factor: A potential target for therapeutics. Trends Cardiovasc Med. 2007, 17: 206-211. 10.1016/j.tcm.2007.06.001.View ArticlePubMedGoogle Scholar
- O'Shea KM, Chess DJ, Khairallah RJ, Hecker PA, Lei B, Walsh K, Des Rosiers C, Stanley WC: Omega-3 polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin. Lipids Health Dis. 2010, 9: 95-10.1186/1476-511X-9-95.View ArticlePubMedPubMed CentralGoogle Scholar
- Taegtmeyer H, Stanley WC: Too much or not enough of a good thing? Cardiac glucolipotoxicity versus lipoprotection. J Mol Cell Cardiol. 2011, 50: 2-5. 10.1016/j.yjmcc.2010.09.014.View ArticlePubMedGoogle Scholar
- Cole MA, Murray AJ, Cochlin LE, Heather LC, McAleese S, Knight NS, Sutton E, Jamil AA, Parassol N, Clarke K: A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. Basic Res Cardiol. 2011, 106: 447-457. 10.1007/s00395-011-0156-1.View ArticlePubMedPubMed CentralGoogle Scholar
- Toime LJ, Brand MD: Uncoupling protein-3 lowers reactive oxygen species production in isolated mitochondria. Free Radical Biol Med. 2010, 49: 606-611. 10.1016/j.freeradbiomed.2010.05.010.View ArticleGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/123/prepub
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