Abstract
Currently, studies in cardiomyopathy and heart failure (HF) were mainly chosen an obese related insulin resistance animal model. However, the CVD morbidity in non‐obese insulin resistance (non‐obese IR) patient was still high. Therefore, it is important to elucidate the different mechanisms in obese and non‐obese IR induced cardiomyopathy/HF. In the study, we have designed obese (45% calorie from fat) and non‐obese (60% calorie from fructose) IR animal models (SD rat). The rats were fed with normal chow, high fat and high fructose diet for 12 weeks. Both obese and non‐obese animal were exhibited insulin resistance syndrome compared with control mice. In addition, obese rat myocardium exhibited severe fibrosis and ROS elevation, hyper‐activation of neurohumoral systems, concentric hypertrophy with slightly impairment of cardiac mechanical performance (Pressure‐Volume catheter), and fewer changes in both plasma and myocardial metabolites profiling (LC‐MS metabolites analysis) compared to non‐obese IR rats. In contrast, cardioyocytes shape change (much leaner and longer), elevation of TUNEL positive signal and higher autophage related proteins expression were co‐contributed in the impairment of cardiac contractility with worse mechanical efficiency in non‐obese IR rats. Both total and phosphorylated cardiac troponin I were downregulated; however, it was upregulation in plasma imply the harmful myocardium damage and HF risk were observed in non‐obese IR animals. Plasma and myocardial metabolites identification suggested LysoPC (18:0) may play a crucial role of cardiomyopathy/HF progression in non‐obese IR group, respectively. LysoPC(18:0) treated neonatal cardiomyocyte trigger cardiomyocyte longer and cell death, which confirmed our hypothesis. In conclusion, this study demonstrated the diverse cardiomyopathy/HF mechanisms in obese and non‐obese IR rats, which may provide a new effective CVD therapeutic target in non‐obese IR patient.
Published Version
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