Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets

Abstract

-The aim of our study was to know whether high dietary energy intake (HDEI) with equilibrated and unbalanced diets in term of lipid composition modify the fatty acid profile of cardiac phospholipids and function of various cardiac cells and to know if the changes in membrane lipid composition can explain the modifications of cellular activity. Wistar rats were fed either a control or high-fat (HF) diet for 12 weeks and Zucker diabetic fatty (ZDF) rats as well as their lean littermate (ZL) a control diet between week 7 to 11 of their life. Energy intake and abdominal obesity was increased in HF-fed and ZDF rats. Circulating lipids were also augmented in both strains although hyperglycemia was noticed only in ZDF rats. HDEI induced a decrease in linoleate and increase in arachidonate in membrane phospholipids which was more pronounced in the ZDF rats compared to the HF-fed rats. In vivo cardiac function (CF) was improved in HF-fed rats whereas ex vivo cardiac function was unchanged, suggesting that environmental factors such as catecholamines stimulated the in vivo CF. The unchanged ex vivo CF was associated with an increased cardiac mass which indicated development of fibrosis and/or hypertrophy. The increased in vivo CF was sustained by an augmented coronary reserve which was related to the cyclooxygenase pathway and accumulation of arachidonate in membrane phospholipids. In conclusion, before triggering a diabetic cardiomyopathy, HDEI stimulated the CF. The development of cardiomyopathy seems to result from fibrosis and/or hypertrophy which augments myocardial stiffness and decreases contractility.Keywords: High dietary energy intake / abdominal adiposity / myocardial function / phospholipid composition / arachidonic acid / coronary reserve Résumé -Évolution du stade de l'activation mécanique jusqu'à la cardiomyopathie chez le rat rendu obèse par des régimes équilibré en graisses ou riche en acides gras saturés et mono-insaturés. Notre objectif a été de savoir si l'excès calorique (EC) modifie la composition en acides gras des phospholipides et la fonction cardiaques et si ces modifications des membranes expliquent les changements d'activité des cellules cardiaques. Des rats Wistar ont été nourris soit avec un régime contrôle, soit avec un régime riche en graisse (RRG) pendant 12 semaines et des rats Zucker diabétiques gras (ZDF) ainsi que leurs homologues maigres (ZL) avec un régime contrôle entre leur 7 e et 11 e semaine de vie. L'ingestion calorique et l'obésité abdominale ont été augmentées chez les rats RRG et ZDF. Une hyperlipidémie a été observée dans les 2 souches, mais l'hyperglycémie n'a été observée que chez les animaux ZDF. L'EC a provoqué une diminution en linoléate et une augmentation en arachidonate dans les membranes cardiaques qui a été plus prononcée chez les rats ZDF. La fonction cardiaque (FC) in vivo a été plus élevée chez les rats RRG malgré une FC ex vivo inchangée. Les catécholamines circulantes pourraient expliquer les discordances. La stabilité de la FC ex vivo a été associée ...

An experimental model of western diet in female Wistar rats leads to cardiac hypoxia related to a stimulated contractility

“…These observations were associated to large modifications of the PUFAs profile of cardiac phospholipids as higher proinflammatory arachidonic acid and lower anti-inflammatory eicosapentaenoic acid proportions were observed in the female rats. Contrasting with our previous data in male rats [21,22], these modifications in membrane lipid composition were not observed in the atria of obese humans, maybe because the composition of the human diet was not controlled as that of the WD.…”

“…We recently observed in WD-fed male rats a higher abdominal fat deposit and in vivo left ventricle developed pressure compared to animals receiving a standard diet [21,22]. For technical reasons, it was not possible to evaluate cardiac mechanical activity in the present study, but our data supported increased intracellular calcium level in the hearts of the WD-fed female rats, without any sign of myocardial apoptosis.…”

“…This stimulation of contractility was confirmed in isolated mitochondria by an activation of oxidative phosphorylation [23]. Experiments in isolated perfused hearts indicated that the phenomenon originated rather from an extra cardiac regulation and it was associated with an improper coronary flow [21,22]. Such effects were associated with an enrichment of cardiac phospholipids with the pro-inflammatory arachidonic acid at the detriment of C18:2 n-6 [21,22].…”

“…Indeed, rats fed with a Western diet (high fat diet or high fat/high sucrose diet) develop abdominal obesity [12,19]. We recently observed in male Wistar rats that the in vivo cardiac mechanical function was increased by an experimental model of Western diet (WD) [21,22]. This stimulation of contractility was confirmed in isolated mitochondria by an activation of oxidative phosphorylation [23].…”

“…Experiments in isolated perfused hearts indicated that the phenomenon originated rather from an extra cardiac regulation and it was associated with an improper coronary flow [21,22]. Such effects were associated with an enrichment of cardiac phospholipids with the pro-inflammatory arachidonic acid at the detriment of C18:2 n-6 [21,22]. These changes in membrane polyunsaturated fatty acids (PUFA) composition led us to hypothesize that a possible pro-inflammatory state of the heart was responsible for some of the observed changes in cardiac function.…”