Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity

Wei Li,Zhuo Liu,Jianxin Wu,Feifei Ma,Shengrong Ouyang,Renqiao Tang

doi:10.1186/s12986-017-0224-0

Abstract

BackgroundFolic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity.MethodsSix-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status.ResultsHFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment.ConclusionFA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Highlights

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia
FA decreased blood glucose and prevented heart enlargement in high-fat diet (HFD) mice To characterize the effects of HFD feeding on phenotype, we examined bodyweight, heart weight, and fasting blood glucose levels
We found a significant increase in fasting blood glucose levels in HFD compared with normal diet (ND), and treatment with the FA markedly decreased blood glucose levels in HFD fed mice (Fig. 1b, p 0.001), but not back to normal level (Fig. 1b, p 0.01)

Summary

Introduction

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. Obesity causes a prevalence of type 2 diabetes and cardiovascular diseases that cause left ventricular (LV) hypertrophy, stroke, and heart failure [3, 4]. Accumulated studies have demonstrated that obesity affects cardiac remodeling with structural and functional abnormalities [5, 6]. Several studies have indicated that oxidative stress plays a pivotal role in the development of obesity-induced cardiomyopathy [10, 11]. Obesity-related hyperglycemia and metabolic abnormalities cause the production of reactive oxygen species (ROS) in vascular cells and cardiomyocytes [12]. During insulin resistance prior to diabetes onset, ROS accumulation can be found in heart tissue [13], contributing to cardiac dysfunction through lipid

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