Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells.

Mi-Kyeong Lee,Mun-Ock Kim,Hyun-Sun Lee,Soo-Yeon Kim,Heung Joo Yuk,Yong-Moon Lee,Myung-Ji Kang,Hyung Won Ryu,Dong-Oh Moon,Eun-Bin Kwon,Sei-Ryang Oh,Su Ui Lee

doi:10.1155/2018/3140267

Abstract

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.

Highlights

Nonalcoholic fatty liver disease (NAFLD), defined by a hepatic TG content exceeding 5% of liver weight, is one of the most common causes of chronic liver disease
Zanthoxylum ailanthoides (ZA)-M treatment with 100 μg/ml for 24 h resulted in a slight inhibition of cell growth
OA reduced cell viability over the 500 μM concentration (approximately 80% versus control group, Figure 1(b)), starting with 500 μM OA exposure induced lipid accumulation (>150% versus vehicle control) in our experiment condition (Figure 1(c)). These results show that cell growth is retarded during excessive lipid accumulation

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), defined by a hepatic TG content exceeding 5% of liver weight, is one of the most common causes of chronic liver disease. NAFLD accompanies various hepatic diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocarcinoma [2, 3]. AMPK, an energy-sensing protein complex, is activated in response to an increase in the AMP:ATP ratio during hypoxia or starvation and upstream kinases including the tumor-suppressor liver kinase B1 (LKB1); the calciumdependent calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) [5,6,7]. Activated AMPK suppresses cleavage processing of sterol regulatory element-binding protein-1c (SREBP-1c) and de novo lipogenesis and stimulates fatty acid oxidation, glucose production, and protein synthesis in the liver [8]. AMPK activators, including metformin and thiazolidinediones (TDZs), have been shown to reduce the hepatic steatosis [9]; their use may be associated with several adverse effects.

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