A high-fructose diet worsens eccentric left ventricular hypertrophy in experimental volume overload

Abstract

Bouchard-Thomassin (LVH) can be affected by diet manipulation. Concentric LVH resulting from pressure overload can be worsened by feeding rats with a high-fructose diet. Eccentric LVH is a different type of hypertrophy and is associated with volume overload (VO) diseases. The impact of an abnormal diet on the development of eccentric LVH and on ventricular function in chronic VO is unknown. This study therefore examined the effects of a fructose-rich diet on LV eccentric hypertrophy, ventricular function, and myocardial metabolic enzymes in rats with chronic VO caused by severe aortic valve regurgitation (AR). Wistar rats were divided in four groups: sham-operated on control diet (SC; n ϭ 13) or fructose-rich diet (SF; n ϭ 13) and severe aortic regurgitation fed with the same diets [aortic regurgitation on control diet (ARC), n ϭ 16, and aortic regurgitation on fructose-rich diet (ARF), n ϭ 13]. Fructose-rich diet was started 1 wk before surgery, and the animals were euthanized 9 wk later. SF and ARF had high circulating triglycerides. ARC and ARF developed significant LV eccentric hypertrophy after 8 wk as expected. However, ARF developed more LVH than ARC. LV ejection fraction was slightly lower in the ARF compared with ARC. The increased LVH and decreased ejection fraction could not be explained by differences in hemodynamic load. SF, ARC, and ARF had lower phosphorylation levels of the AMP kinase compared with SC. A fructose-rich diet worsened LV eccentric hypertrophy and decreased LV function in a model of chronic VO caused by AR in rats. Normal animals fed the same diet did not develop these abnormalities. Hypertriglyceridemia may play a central role in this phenomenon as well as AMP kinase activity. cardiomyopathy; metabolic syndrome; heart hypertrophy; triglycerides; glucose; fatty acids CHRONIC LEFT VENTRICULAR VOLUME overload (VO) causes severe left ventricular dilatation and eccentric hypertrophy. This type of left ventricular hypertrophy is encountered mainly in patients with valvular diseases such as chronic mitral or aortic valve regurgitation (AR). AR is associated with a long asymptomatic period during which the left ventricle (LV) progressively dilates and hypertrophies. In parallel with the LV dilatation, systolic function slowly decreases and symptoms eventually appear (4, 5). Although it is not the most frequent valvular disease in Western countries, it has been estimated based on the Framingham study that 13% of the population suffer from AR of varying degrees of severity (40).No drug treatment has proved to be effective to decrease morbidity or mortality or delay the evolution toward heart failure or valve replacement surgery in patients with chronic VO from valve disease (5). The search for an effective treatment is still ongoing. Patient lifestyle has a significant impact on the evolution of many cardiac diseases. Whereas good habits such as exercising and eating low fat/low sugar diets seem beneficial, a lack of physical activity and eating imbalanced diets may act in the opposite way. ...

Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation

“…MTORC1 activation happened very quickly (2 days) after induction of severe LV VO. Our results at 8 weeks are in line with those we obtained in a recent study where we observed that S6K (mTORC1) and Akt S473 (mTORC2) levels were unchanged at 8 weeks in this model (Bouchard-Thomassin et al 2011 ). At 6 months, we previously reported that Akt S473 phosphorylation was increased suggesting that mTORC2 becomes activated.…”

Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation

“…MTORC1 activation happened very quickly (2 days) after induction of severe LV VO. Our results at 8 weeks are in line with those we obtained in a recent study where we observed that S6K (mTORC1) and Akt S473 (mTORC2) levels were unchanged at 8 weeks in this model (Bouchard-Thomassin et al 2011 ). At 6 months, we previously reported that Akt S473 phosphorylation was increased suggesting that mTORC2 becomes activated.…”

Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

“…The present study, however, supports the deleterious effect of long term high fructose feeding on ischemic-reperfusion injury, caused by impaired normal endothelial function, induction of oxidative stress and systemic inflammation [27,48,63,64]. The results obtained in the present study thus imply an important role of NOS in high fructose diet induced IRS [14,48] and also in atorvastatin mediated protection against ischemia-reperfusion injury.…”

Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism

“…This has been observed in another model of eccentric LVH (mitral regurgitation in dogs) [ 32 ]. We reported in a previous study that the myocardial triglycerides content in 8-week AR rats was unchanged [ 12 ] and we did not observe positive staining for lipids using the oil red O method on LV section of 6-month AR rats (unpublished observation).…”

Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation

“…MTORC1 activation happened very quickly (2 days) after induction of severe LV VO. Our results at 8 weeks are in line with those we obtained in a recent study where we observed that S6K (mTORC1) and Akt S473 (mTORC2) levels were unchanged at 8 weeks in this model (Bouchard-Thomassin et al 2011 ). At 6 months, we previously reported that Akt S473 phosphorylation was increased suggesting that mTORC2 becomes activated.…”

Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

“…The present study, however, supports the deleterious effect of long term high fructose feeding on ischemic-reperfusion injury, caused by impaired normal endothelial function, induction of oxidative stress and systemic inflammation [27,48,63,64]. The results obtained in the present study thus imply an important role of NOS in high fructose diet induced IRS [14,48] and also in atorvastatin mediated protection against ischemia-reperfusion injury.…”

Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism

“…This has been observed in another model of eccentric LVH (mitral regurgitation in dogs) [ 32 ]. We reported in a previous study that the myocardial triglycerides content in 8-week AR rats was unchanged [ 12 ] and we did not observe positive staining for lipids using the oil red O method on LV section of 6-month AR rats (unpublished observation).…”

Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation

“…MTORC1 activation happened very quickly (2 days) after induction of severe LV VO. Our results at 8 weeks are in line with those we obtained in a recent study where we observed that S6K (mTORC1) and Akt S473 (mTORC2) levels were unchanged at 8 weeks in this model (Bouchard-Thomassin et al 2011 ). At 6 months, we previously reported that Akt S473 phosphorylation was increased suggesting that mTORC2 becomes activated.…”

Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

“…The present study, however, supports the deleterious effect of long term high fructose feeding on ischemic-reperfusion injury, caused by impaired normal endothelial function, induction of oxidative stress and systemic inflammation [27,48,63,64]. The results obtained in the present study thus imply an important role of NOS in high fructose diet induced IRS [14,48] and also in atorvastatin mediated protection against ischemia-reperfusion injury.…”

Transcriptional Changes Associated with Long-Term Left Ventricle Volume Overload in Rats: Impact on Enzymes Related to Myocardial Energy Metabolism

“…This has been observed in another model of eccentric LVH (mitral regurgitation in dogs) [ 32 ]. We reported in a previous study that the myocardial triglycerides content in 8-week AR rats was unchanged [ 12 ] and we did not observe positive staining for lipids using the oil red O method on LV section of 6-month AR rats (unpublished observation).…”