Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.

Shiau-Huei Huang,Charng-Cherng Chyau,Robert Y Peng,Wen-Juan Zhang,Chun-Chao Chang,Hsueh-Fang Wang,Chin-Chu Chen

doi:10.3390/ijms21010360

Abstract

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

Highlights

Patient with non-alcoholic fatty liver disease (NAFLD) implies a state of excessive fat built-up in livers with, or without minimal inflammation [1,2,3,4]
A high dose Antrodan cotreatment in high-fructose diet (HFD) significantly suppressed the bodyH- aFnDdsliigvneirf-iwcaenigtlhytsi,nacnredatsheedrtahteiobloivdeyr-watn/dboldivyewr-wt, ebieginhgtsmoformeiecffe.ecTthiveebtohdany-thaendpolisviteirv-ewceoingthrtosl ‘aOnrdlisthtaet’r(aTtaioblleiv1e)r. wt/body wt in the Antrogen (40 mg/kg) control group remained normal as the control (Table 1)
Dietary supplementation from fermentation products may be used as strategies for preventing or alleviating the fatty liver symptoms

Summary

Introduction

Patient with non-alcoholic fatty liver disease (NAFLD) implies a state of excessive fat built-up in livers with, or without minimal inflammation [1,2,3,4]. NAFLD is the hepatic manifestation of the metabolic syndrome associated with obesity [5]. High fructose consumption (HFC) leads to increased body weight with elevated systolic blood pressure, blood glucose, insulin, and serum triglyceride (TG) levels [7]. HFC reduces energy expenditure, thereby causing obesity, adipocyte hypertrophy, and inflammation [8]; lipid spillover further causes hepatic steatosis, peripheral insulin resistance and diabetes, raised levels of LDL and a decrease in HDL [9]. A high-fructose and high-fat diet potentially tends to damage liver mitochondria, increasing the risk from fatty-liver disease and metabolic syndrome [8]

Results

Discussion

Conclusion