Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats

Abstract

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.