Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder characterized by an enhanced accumulation of lipids, which affects around 40% of the world’s population. The T. fuciformis fungus possesses immunomodulatory activity and other beneficial properties that may alleviate steatosis through a different mechanism. The present study was designed to evaluate the effect T. fuciformis crude polysaccharides (TFCP) on inflammatory and lipid metabolism gene expression, oxidative stress, and lipid profile. Mice were divided into groups receiving (a) a normal chow diet (NCD), (b) a methionine–choline-deficient (MCD) diet, and (c) a MCD diet with TFCP. Liver histopathology was performed, and the hepatic gene expression levels were estimated using qRT-PCR. The lipid profiles, ALT, AST, and efficient oxidative enzymes were analyzed using ELISA. The TFCP administration in the MCD-fed mice suppressed hepatic lipid accumulation, lipid metabolism-associated genes (HMGCR, FABP, SREBP, ACC, and FAS), and inflammation-associated genes (IL-1β, TLR4, TNF-α, and IL-6) whilst enhancing the expression of HNF4α genes. TFCP mitigated against oxidative stress and normalized healthy lipid profiles. These results highlighted that TFCP prevents NAFLD through the inhibition of oxidative stress and inflammation, suggesting TFCP would potentially be an effective therapeutic agent against NAFLD progression.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD) is a severe hepatic disorder causing a huge overall burden of liver diseases [1]

  • NAFLD may be defined as the umbrella term covering a range of abnormalities, from NAFLD to nonalcoholic steatohepatitis (NASH), which may progress to fibrosis and cirrhosis [1]

  • The abnormalities that develop in NAFLD patients include (i) abdominal obesity, (ii) high blood pressure, (iii) high blood glucose, (iv) high serum triglycerides, and (v) a low abundance of serum high-density lipoprotein cholesterol (HDL-C), which was reported to contribute significantly to the disease [2]

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a severe hepatic disorder causing a huge overall burden of liver diseases [1]. Have been found to extend their axes bi-directionally (i.e., endocrine and immunological pathways) with numerous extra-intestinal organs, such as the brain, kidneys, and bone [4] This gut–liver axis plays an essential role during the progression of chronic liver diseases, such as hepatitis B and C, NAFLD, NASH, and hepatocellular carcinoma (HCC) [6]. Considering the above background, this study was designed to investigate the effects of TFCP on intrinsic immunogenic and metabolic activities in methionine–choline-deficient (MCD) mice with diet-induced NAFLD. We studied the impact of TFCP on the serum parameters, including lipid profile, antioxidants, liver enzymes (ALT and AST), and the gene expression of inflammatory cytokines (IL-1β, HNF4α, TLR4, TNF-α, and IL-6) and lipid metabolism-associated genes (HMGCR, FABP, SREBP, ACC, and FAS) in the MCDdiet-induced NAFLD mice. Our results indicated that TFCP could help to alleviate NAFLD by suppressing inflammation

TFCP Preparation and Characterization
Animal Experiments
Collection of Liver Tissue and Their Histopathological Analysis
Serum and Blood Measurements
Real-Time Quantitative Polymerase Chain Reaction
Inhibition of Hepatic Steatosis and Reduction in Liver Weight through TFCP Administration
Effects of TFCP on Triglyceride (TG), Total Cholesterol (TC), and High-Density
TFCP Administration Reduced the Expression of the Genes Involved in Cholesterol Metabolism and Transport
TFCP Administration Reduces the Expression of Lipid-Metabolism-Associated Genes
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