Bai-Hu-Jia-Ren-Shen-Tang Decoction Reduces Fatty Liver by Activating AMP-Activated Protein Kinase In Vitro and In Vivo.

Hui-Kang Liu,I-Jung Lee,Lie-Chwen Lin,Tzu-Min Hung,Hsiu-Chen Huang,Chia-Chuan Chang,Jing-Jy Cheng,Cheng Huang

doi:10.1155/2015/651734

Abstract

Obesity and associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. In Asian traditional medicine, Bai-Hu-Jia-Ren-Shen-Tang (BHJRST) is widely used in diabetes patients to reduce thirst. However, whether it has a therapeutic effect on T2DM or NAFLD is not known. The aim of this study was to examine whether BHJRST had a lipid-lowering effect using a HuS-E/2 cell model of fatty liver induced by palmitate and in a db/db mouse model of dyslipidemia. Incubation of HuS-E/2 cells with palmitate markedly increased lipid accumulation and expression of adipose triglyceride lipase (ATGL), which is involved in lipolysis. BHJRST significantly decreased lipid accumulation and increased ATGL levels and phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream target, acetyl-CoA carboxylase (ACC), which are involved in fatty acid oxidation. Furthermore, after twice daily oral administration for six weeks, BHJRST significantly reduced hepatic fat accumulation in db/db mice, as demonstrated by increased hepatic AMPK and ACC phosphorylation, reduced serum triglyceride levels, and reduced hepatic total lipid content. The results show that BHJRST has a lipid-lowering effect in the liver that is mediated by activation of the AMPK signaling pathway.

Highlights

Obesity and dysregulated insulin action in the liver are strongly associated and are currently a worldwide health problem [1]
Adipose triglyceride lipase (ATGL) and hormonesensitive lipase (HSL) are the major triglyceride lipases in many tissues [10] and expression of both is decreased in the obese, insulin-resistant state, suggesting that insulin resistance is associated with impaired lipolysis [11, 12]
To determine whether liver cells esterify and deposit fatty acid as lipid droplets, HuS-E/2 immortalized human primary hepatocytes were incubated in glucose-free PH medium alone or containing 0.05–1 mM palmitate; intracellular lipid accumulation was measured using oil Red O staining

Summary

Introduction

Obesity and dysregulated insulin action in the liver are strongly associated and are currently a worldwide health problem [1]. The molecular mechanisms underlying fatty liver are not fully understood, dysregulation of hepatic lipid homeostasis caused by pathological conditions, such as reduced fatty acid oxidation, enhanced de novo lipogenesis, elevated hepatic fatty acid influx, and/or increased systemic insulin resistance, is thought to be important in its development [5]. Current therapies for fatty liver disease are aimed at reducing body weight and improving insulin sensitivity to alleviate the associated metabolic syndrome [6, 7]. Activation of AMPK by phosphorylation of threonine 172 switches off fatty acid synthesis by increasing the phosphorylation and inactivation of acetyl-CoA carboxylase

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Conclusion