Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. In this study, the ability of Grifola frondosa heteropolysaccharide (GFP) to ameliorate NAFLD was investigated in rats fed a high-fat diet (HFD). The molecular mechanisms modulating the expression of specific gene members related to lipid synthesis and conversion, cholesterol metabolism, and inflammation pathways were determined. The components of the intestinal microflora in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Supplementation with GFP significantly increased the proportions of Allobaculum, Bacteroides, and Bifidobacterium and decreased the proportions of Acetatifactor, Alistipes, Flavonifractor, Paraprevotella, and Oscillibacter. In addition, Alistipes, Flavonifractor, and Oscillibacter were shown to be significant cecal microbiota according to the Spearman’s correlation test between the gut microbiota and biomedical assays (|r| > 0.7). Histological analysis and biomedical assays showed that GFP treatments could significantly protect against NAFLD. In addition, Alistipes, Flavonifractor, and Oscillibacter may play vital roles in the prevention of NAFLD. These results suggest that GFP could be used as a functional material to regulate the gut microbiota of NAFLD individuals.

Highlights

  • A high-fat diet (HFD) is a risk factor for a range of diseases, including lipid metabolism disorders (LMDs), non-alcoholic fatty liver disease (NAFLD), and type-2 diabetes (T2D) [1,2]

  • The bodyweight gain of animals in the Grifola frondosa heteropolysaccharide (GFP) group (154.33 ± 32.75 g) was significantly lower than that in the HFD group after eight weeks (p < 0.01), while there was no significant difference between the GFP and control diet (NFD) group.Increased alanine transaminase (ALT), serum aspartate transaminase (AST) lipid triglycerides (TG), and total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) concentrations and decreased liver glutathione peroxidase (GSH-Px), and liver superoxide dismutase (SOD) and the levels of high-density lipoprotein cholesterol (HDL-C) concentrations were the primary features of NAFLD status of rats in the HFD group [21]

  • GFP was shown to significantly attenuate this process in all respects, except for ALT levels (Figure 1). These results indicate the ability of GFP to improve the obesity, liver function, and lipid levels of NAFLD rats

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Summary

Introduction

A high-fat diet (HFD) is a risk factor for a range of diseases, including lipid metabolism disorders (LMDs), non-alcoholic fatty liver disease (NAFLD), and type-2 diabetes (T2D) [1,2]. The majority of NAFLD patients do not recover from this condition; rather, the disease progresses to non-alcoholic steatohepatitis (NASH), hepatocyte fibrosis, cirrhosis, or even hepatocellular carcinoma which are responsible for most deaths worldwide [4]. Some clinical data have shown that the composition and characteristics of the intestinal flora in patients with metabolic disorders differ from those in normal populations [7,8]. It is necessary to search for a novel drug or natural compound without any side effects and find out how the compound relates to the intestinal flora in the treatment of NAFLD. The intestinal flora may be a major factor in the mechanisms of the polysaccharides and the relationship between the effect of polysaccharides and intestinal flora in the treatment of NAFLD still remains to be further studied

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