Heat-Killed Enterococcus faecalis EF-2001 Attenuate Lipid Accumulation in Diet-Induced Obese (DIO) Mice by Activating AMPK Signaling in Liver.

Meiqi Fan,Nishala Erandi Wedamulla,Eun-Kyung Kim,Kwon Il Han,Young-Jin Choi,Ji-Young Hwang,Yujiao Tang

doi:10.3390/foods11040575

Abstract

To explore the inhibitory mechanism of heat-killed Enterococcus faecalis, EF-2001 on hepatic lipid deposition, a diet-induced obese (DIO) animal model was established by high-fat diet (HFD). The DIO C57BL/6 mice were divided into four groups: the normal group without HFD (ND, n = 8), obesity group (HFD, n = 8), experimental group (HFD + EF-2001, 200 mg/kg, n = 8), and positive control group (HFD + Orlistat, 60 mg/kg, n = 8). After 4 weeks, liver and adipose tissue were fixed in 10% paraformaldehyde, followed by embedding in paraffin for tissue sectioning. The differences in body mass, body fat ratio, fatty cell area, and lipid profiling of the liver (TC, LDL, and HDL) were also determined. Moreover, Western blot was performed to analyze the expression of lipid accumulation-related proteins, including AMPK, PPARγ, SREBP-1, ACC, and FAS. Compared with the HFD group, the HFD + EF-2001 group exhibited decreased fat mass, liver index, adipocyte area, TC, and LDL, and an increased level of HDL. The results of liver hematoxylin and eosin (H&E), and oil red O staining showed that the mice in each intervention group were improved on hepatic lipid accumulation, and the mice in the HFD + EF-2001 group were the most similar to those in the normal group when compared with the HFD group. From the Western blot results, we proved that EF-2001 activated the AMPK signaling pathway. EF-2001 significantly upregulated the expressions of p-AMPK and p-ACC and downregulated PPARγ, SREBP-1, and FAS in murine liver. Taken together, these results suggest that EF-2001 decrease lipid accumulation in the DIO model mice through the AMPK pathway and ameliorate liver damage by HFD.

Highlights

With the increasing proportion of high-calorie diets in the dietary composition of the population, the rate of overweight and obesity is rising [1]
Homeostatic regulation of lipid metabolism is fundamental to maintaining the basic functions of the body, and disorders of lipid metabolism play a significant role in the development of diabetes, obesity, fatty liver, cardiovascular disease, and abnormal cell proliferation [3,4,5]
We examined the effects of EF-2001 on hepatic lipid accumulation in diet-induced obese (DIO) mice and examined the effects of TG synthesis, catabolism, and the AMPK signaling pathway to provide a new theoretical basis for the treatment of disorders of hepatic lipid metabolism

Summary

Introduction

With the increasing proportion of high-calorie diets in the dietary composition of the population, the rate of overweight and obesity is rising [1]. A long-term high-fat diet may cause the energy intake of the body to exceed its energy consumption, and the excess energy will be stored as body fat, eventually leading to obesity and lipid metabolism disorders [2]. Since non-alcoholic fatty liver disease (NAFLD) has been associated with obesity, chronic oxidative stress, dyslipidemia, and inflammation, NAFLD has been viewed as a hepatic manifestation of metabolic syndrome [6]. There are some hepatoprotective, enzyme-lowering, and lipid-lowering drugs for symptomatic management [8,9]. Most of these drugs are associated with adverse side effects. E. faecalis is effective in treating hyperlipidemia, obesity, and fatty liver disease [13]

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Results

Conclusion