Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats.

Xue Wu,Huijuan Luo,Minyao Li,Nan Xu,Yucui Li,Qionghui Huang,Liping Chen,Jiazhen Wu,Xiaoqi Huang,Yuhong Liu,Yuxuan Gan,Ziren Su

doi:10.3389/fphar.2019.01134

Abstract

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

Highlights

Nonalcoholic fatty liver disease (NAFLD), a result of the pandemic of obesity and diabetes, has become a leading cause of liver disease and emerged a major challenge in modern society
Chronic exposure to high fat diet (HFD) disturbed lipid homeostasis in a time-dependent manner leading to development of NAFLD
Vitamin E (VE) and Patchouli alcohol (PA) supplementation for 4 weeks markedly decreased vacuoles, lipid droplets area, and inflammation in the liver of HFD-fed rats. These results indicated that PA was effective in reducing HFD-induced body weight gain and preventing hepatic steatosis in rats

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), a result of the pandemic of obesity and diabetes, has become a leading cause of liver disease and emerged a major challenge in modern society. It affects 6–45% of the general population worldwide with highly prevalence and incidence (Fazel et al, 2016). When the rate of hepatic lipid uptake exceeds the rate of lipid disposal, lipid accumulates in the liver and results in steatosis (Ipsen et al, 2018). A dysregulation in VLDL uptake, export, or synthesis is one of the major causes of hepatic steatosis (As, 2018). Current studies have demonstrated that endoplasmic reticulum (ER) stress is implicated in the inhibition of VLDL

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