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

Evangelia Mourmoura,Kasra Azarnoush,Valérie Chaté,Luc Demaison,Karine Couturier,Corinne Malpuech-Brugère

doi:10.1051/ocl/2015008

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.

Highlights

Obesity is associated with increased risk of cardiovascular diseases (Mathers and Loncar, 2006) and improved survival after myocardial infarction and stroke (Romero-Corral et al, 2006)
After analysis of the fatty acid composition of the diets, we found that the standard diet contained 24% of saturated fatty acids (SFAs), 23% of monounsaturated fatty acids (MUFAs), 48% of n-6 polyunsaturated fatty acids (PUFAs) and 4.5% of n-3 PUFAs while the HF diet contained 37% of SFAs, 46% of MUFAs, 15% of n-6 PUFAS and 1.2% of n-3 PUFAs
In order to know whether this increased cardiac function was due to the heart itself related to the increased AA proportion in membrane lipids or to environmental factors, we evaluated the cardiac function in the ex vivo situation

Summary

Introduction

Obesity is associated with increased risk of cardiovascular diseases (Mathers and Loncar, 2006) and improved survival after myocardial infarction and stroke (Romero-Corral et al, 2006). The progression of cardiac function during the development of obesity has been clearly characterized in animal models of postnatal overfeeding. Post-natal overfeeding is achieved in mice and rats by drastically decreasing the number of pups in a litter. The effects of high-fat diet-induced abdominal obesity on cardiac function have been studied ex vivo in different models of perfused hearts (Marciniak et al, 2014; Burgmaier et al, 2010). The results from those studies clearly show that ex vivo cardiac function is rapidly reduced soon after the beginning of the high-fat (HF) diet. Discrepancies between the in vivo and ex vivo measurements at the onset of obesity necessitates further investigation before a definitive conclusion can be drawn

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