Simvastatin and Bezafibrate ameliorate Emotional disorder Induced by High fat diet in C57BL/6 mice

Hui Wang,Jia Zhou,Lu Lu Wang,Qiong Zhen Liu,Jing Shang

doi:10.1038/s41598-017-02576-5

Abstract

High fat diet (HFD)-induced metabolic disorders may lead to emotional disorders. This study aimed to explore the effect of simvastatin (SMV) and bezafibrate (BZ) on improving HFD-induced emotional changes, and tried to identify their different mechanisms. The intraperitoneal glucose tolerance test (IPGTT) was used to evaluate glucose control ability; and behavior tests including open field tests (OFT), forced swimming tests (FST), tail suspension tests (TST) and sucrose preference (SPT), were then performed to evaluate emotional changes. Serum samples were collected for the LC-MS based metabolomics analysis to explore the emotional-related differential compounds; we then evaluated the effect of the drugs. The abnormal serum metabolic profiling and emotional changes caused by HFD in mice was alleviated by SMV treatment, whereas BZ only affected the emotional disorder. The improvement of cannabinoid analogues and then produced influences on the endocannabinoid system, which may be a potential mechanism SMV action. BZ promoted tryptophan-serotonin pathway and inhibited tryptophan-kynurenine pathway, which may be its mechanism of action. Here, we proposed a shed light on the biological mechanisms underlying the observed effects, and identified an important drug candidate for the treatment of emotional disorders induced by HFD.

Highlights

According to a systematic and global analysis in children and adults from 1980–2013, the overweight and obese population has reached nearly 2.1 billion wordwide[1]
We found that the animals fed with a High fat diet (HFD) showed significant high body weights compared to the normal diet group (P < 0.01)
The areas under the curve (AUC) for the glycaemia over the 120 min time period is represented in Fig. 1F; the AUC in the HFD group significantly increased compared to the ND group (P < 0.001)

Summary

Introduction

According to a systematic and global analysis in children and adults from 1980–2013, the overweight and obese population has reached nearly 2.1 billion wordwide[1]. SMV has been reported to show some cholesterol-independent effects that include anti-inflammatory, anti-oxidative and neuro-protective properties[9]. It can cross the blood-brain barrier (BBB) and exert some serious adverse effects on neurons as a lipophilic drug[10]. Clinical studies regarding the effects of statins on depression are incongruous, and statistical data show that the use of SMV after a cardiac intervention is associated with a reduced risk of subsequent depression[11]. Little is known about metabolite changes in HFD-induced-emotional disorder mice with drug intervention. An LC MS-based serum metabolomics analysis coupled with behavioral tests was performed to elucidate the underlying mechanism of drug intervention (BZ and SMV) for improving emotional changes induced by HFD

Objectives

Methods

Results

Conclusion