Abstract 760: Metabolic Syndrome Impairs Cardiac Remodeling During Pregnancy in Mice

Abstract

Rationale: Due to the change of life style in the past decades, the incidence of metabolic syndrome (MetS) and obesity in women of childbearing age has been increased. Evidences have shown that complications during pregnancy, such as obesity and gestational diabetes, strongly link to future heart diseases. During normal pregnancy, the heart undergoes a physiological remodeling with mild ventricular dilation and hypertrophy. However, the effects of MetS on cardiac phenotype during pregnancy are not well understood. Moreover, animal models for MetS so far are not well established, which are usually species limited, gender limited and lack of translational significance. Thus, it’s important to develop an animal model which resembles the etiology of MetS in human beings. Objective: Establish a model of MetS in female C57BL/6J mice and determine the effects of MetS on cardiac remodeling during pregnancy. Methods and Results: To establish a mouse model of MetS, high fat (49% kcal)/high carbohydrates (HF-HC) diet were given to C57BL/6J female mice at the age of 8-week. Mice fed with normal diet (10% kcal fat) served as control. After 14 weeks feeding, mice fed with HF-HC diet showed significantly higher body weight and gonadal fat weight compared with control mice. Moreover, mice fed with HF-HC diet showed impaired glucose tolerance and higher serum total cholesterol level. The symptoms of obesity, impaired glucose tolerance and dyslipidemia suggest the development of MetS. Female mice after 14-week special diet feeding were subjected to breeding. Cardiac function was evaluated by echocardiography during pregnancy and 1-day post-partum, then the mice were terminated 1-day post-partum. Female mice that developed MetS showed impaired cardiac function and pathological remodeling during pregnancy. Moreover, mice fed with HF-HC diet showed more myocardium interstitial fibrosis accompanied with upregulation of fibrosis related genes in the heart compared with Ctrl diet. Conclusion: We’ve developed a mouse model of MetS in C57BL/6J mice strain with 14 weeks feeding of HF-HC diet, which resemble the western diet that affects human beings nowadays. Females that have MetS showed impaired cardiac function and pathological remodeling during pregnancy.