Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2017; 23(21): 3805-3814
Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3805
Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats
Yi Tan, Jane Kim, Jing Cheng, Madeleine Ong, Wei-Guo Lao, Xing-Liang Jin, Yi-Guang Lin, Linda Xiao, Xue-Qiong Zhu, Xian-Qin Qu
Yi Tan, Jane Kim, Jing Cheng, Madeleine Ong, Wei-Guo Lao, Xing-Liang Jin, Yi-Guang Lin, Linda Xiao, Xue-Qiong Zhu, Xian-Qin Qu, School of Medical and Molecular Biosciences, University of Technology Sydney, NSW 2007, Australia
Jing Cheng, Xing-Liang Jin, Xue-Qiong Zhu, Xian-Qin Qu, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 32527, Zhejiang Province, China
Author contributions: Tan Y, Qu XQ and Zhu XQ substantially contributed to the conception and design of the study; Tan Y, Kim J, Cheng J, Ong M, Lao WG, Jin XL, Lin YG, Xiao L contributed to acquisition, analysis and interpretation of data; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Institutional review board statement: All procedures in animal study were reviewed and approved by the Animal Care and Ethics Committee of the University of Technology Sydney.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the University of Technology Sydney Animal Ethics Committee (UTS ACEC 2009-325A), following guidelines issued by the National Health and Medical Research Council of Australia.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Xianqin.qu@uts.edu.au. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xian-Qin Qu, PhD, MD, School of Medical and Molecular Biosciences, University of Technology Sydney, 15 Broadway, NSW 2007, Australia. xianqin.qu@uts.edu.au
Telephone: +61-2-95147852 Fax: +61-2-95147852
Received: January 23, 2017
Peer-review started: January 27, 2017
First decision: March 3, 2017
Revised: March 13, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: June 7, 2017
Processing time: 134 Days and 21.5 Hours
Abstract
AIM

To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats.

METHODS

Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c).

RESULTS

Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels (both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172 (P < 0.05) and phosphorylated ACC and SREBP1c (both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats.

CONCLUSION

The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

Keywords: Non-alcoholic fatty liver disease; Green tea polyphenols; Hepatic lipogenesis; Inflammatory cytokines; AMP-activated protein kinase

Core tip: The aim of this study was to examine the protective effects and molecular mechanism of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD)-induced by high fat diet (HFD) in genetically obese Zucker fatty (ZF) rats. The data of the study has demonstrated: (1) HFD-ZF rats is an optimal rodent model of NAFLD for testing novel/natural agents for this disease; (2) GTP treatment ameliorated metabolic and histopathological abnormalities in HFD-ZF rats with NAFLD; and (3) GTP exerted a protective effect against hepatic steatosis and liver injury by attenuating inflammatory cytokines and inhibiting lipogenesis through upregulating AMPK activation. Therefore, GTP proves to be an effective natural agent for preventing NAFLD and reducing the risk of its severe complications such as nonalcoholic steatohepatitis, cirrhosis and hepatic cellular carcinoma.