Chinese olive extract ameliorates hepatic lipid accumulation in vitro and in vivo by regulating lipid metabolism

Yu-Te Yeh,Yan-Yu Cho,An-Na Chiang,Shu-Chen Hsieh

doi:10.1038/s41598-018-19553-1

Abstract

Chinese olive contains plenty of polyphenols, which possess a wide range of biological actions. In this study, we aimed to investigate the role of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) in the modulation of lipid accumulation in vitro and in vivo. In cellular studies, CO-EtOAc attenuated oleic acid-induced lipid accumulation; we then elucidated the molecular mechanisms of CO-EtOAc in FL83B mouse hepatocytes. CO-EtOAc suppressed the mRNA levels of fatty acid transporter genes (CD36 and FABP) and lipogenesis genes (SREBP-1c, FAS, and ACC1), but upregulated genes that govern lipolysis (HSL) and lipid oxidation (PPARα, CPT-1, and ACOX). Moreover, CO-EtOAc increased the protein expression of phosphorylated AMPK, ACC1, CPT-1, and PPARα, but downregulated the expression of mature SREBP-1c and FAS. AMPK plays an essential role in CO-EtOAc-mediated amelioration of lipid accumulation. Furthermore, we confirmed that CO-EtOAc significantly inhibited body weight gain, epididymal adipose tissue weight, and hepatic lipid accumulation via regulation of the expression of fatty acid transporter, lipogenesis, and fatty acid oxidation genes and proteins in C57BL/6 mice fed a 60% high-fat diet. Therefore, Chinese olive fruits may have the potential to improve the metabolic abnormalities associated with fatty liver under high fat challenge.

Highlights

Chinese medicinal herbs and phytochemicals are known to play a major role in the discovery of new therapeutic agents and have received much attention as sources of bioactive substances including anti-oxidative, hypoglycaemic and hypolipidemic agents[1,2]
CO-EtOAc up-regulated the mRNA levels of genes involved in lipolysis (HSL) and lipid oxidation, such as PPARα, carnitine palmitoyltransferase-1 (CPT-1), and Acyl-CoA oxidase (ACOX). These findings show that CO-EtOAc exhibits a broad range of biological actions, which may include the modulation of fatty acid transport, de novo lipogenesis, and lipid oxidation
In order to confirm the mechanism by which CO-EtOAc can attenuate high-fat diet (HFD)-induced lipid accumulation as shown in the cellular model, we investigated genes involved in fatty acid transport, de novo lipogenesis and lipid oxidation

Summary

Introduction

Chinese medicinal herbs and phytochemicals are known to play a major role in the discovery of new therapeutic agents and have received much attention as sources of bioactive substances including anti-oxidative, hypoglycaemic and hypolipidemic agents[1,2]. Understanding the regulation of these enzymes that control lipolysis would be likely the essential targets for contribution to lipid metabolism Another mechanism that has been postulated to contribute to lipid disorders is defective fatty acid oxidation. Activation of PPARα could ameliorate hepatic insulin resistance and protect the liver from NAFLD and NASH by promoting the target genes related to fatty acid oxidation[34,35]. Activation of AMPK has the potential to switch cells from an anabolic to a catabolic state, initiating an ATP-producing pathway, increasing fatty acid oxidation, and inhibiting hepatic lipogenesis[39,40]. AMPK modulates SREBP-1c and PPARα, which play essential roles in the regulation of gene products responsible for the synthesis of cholesterol, fatty acids, and triglycerides in the liver[41,42]. The effects of AMPK activation provides rationale for the development of new pharmacological therapies and nutritional supplements to reverse metabolic disorders[43,44]

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