Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2015; 21(26): 8061-8072
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8061
Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats
Xiang Qiu, Dan-Hong Gao, Xiao Xiang, Yu-Fang Xiong, Teng-Shi Zhu, Lie-Gang Liu, Xiu-Fa Sun, Li-Ping Hao
Xiang Qiu, Dan-Hong Gao, Xiao Xiang, Yu-Fang Xiong, Teng-Shi Zhu, Lie-Gang Liu, Xiu-Fa Sun, Li-Ping Hao, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Xiang Qiu, Dan-Hong Gao, Xiao Xiang, Yu-Fang Xiong, Teng-Shi Zhu, Lie-Gang Liu, Xiu-Fa Sun, Li-Ping Hao, Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Xiang Qiu, Dan-Hong Gao, Xiao Xiang, Yu-Fang Xiong, Teng-Shi Zhu, Lie-Gang Liu, Xiu-Fa Sun, Li-Ping Hao, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Yu-Fang Xiong, Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Hao LP, Gao DH and Qiu X conceived and designed the research; Qiu X, Gao DH and Zhu TS performed the experiments; Qiu X and Gao DH analyzed the data; Qiu X and Xiong YF prepared the figures; Qiu X and Xiang X prepared the manuscript; Hao LP, Liu LG and Sun XF supervised the work, evaluated the data, wrote the manuscript, and corrected the manuscript for publication; all authors read and approved the final manuscript.
Supported by Grants from the National High Technology Research and Development Program of China, No. 2010AA023003 and the National Natural Science Foundation of China, No. NSFC-81172657.
Institutional review board statement: All experiments were approved by the Tongji Medical College Council’s Animal Care Committee.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee at Tongji Medical College, Huazhong University of Science and Technology (IACUC protocol number: 373).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: 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: Li-Ping Hao, MD, PhD, Associate Professor, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. haolp@mails.tjmu.edu.cn
Telephone: +86-27-83650523 Fax: +86-27-83693307
Received: January 15, 2015
Peer-review started: January 15, 2015
First decision: February 10, 2014
Revised: March 4, 2015
Accepted: April 28, 2015
Article in press: April 28, 2015
Published online: July 14, 2015
Abstract

AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism.

METHODS: After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses.

RESULTS: Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with lipid metabolism and insulin signaling.

CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.

Keywords: Lutein, Non-alcoholic fatty liver disease, Insulin resistance, Sirtuin 1, Peroxisome proliferators activated receptor-α

Core tip: Lutein has potential positive effects on chronic diseases. To date, no previous studies have reported the regulatory effects of lutein on non-alcoholic fatty liver disease (NAFLD). We observed that lutein has positive effects on hepatic lipid accumulation, liver function, and insulin resistance induced by a high-fat diet, possibly via activation of the expression of sirtuin 1 and, subsequently, peroxisome proliferators activated receptor-α, and other key factors in insulin signaling. These findings provide a new prospect for preventing NAFLD.