Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2019; 25(8): 955-966
Published online Feb 28, 2019. doi: 10.3748/wjg.v25.i8.955
Procyanidin B2 protects against diet-induced obesity and non-alcoholic fatty liver disease via the modulation of the gut microbiota in rabbits
Ya-Wei Xing, Guang-Tao Lei, Qing-Hua Wu, Yu Jiang, Man-Xiang Huang
Ya-Wei Xing, Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Guang-Tao Lei, Qing-Hua Wu, Yu Jiang, Man-Xiang Huang, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Lei GT designed the research; Xing YW performed the research; Wu QH funded the research; Jiang Y and Huang MX analyzed and interpreted the data; Xing YW wrote the paper.
Supported by Major Projects of Science and Technology in Jiangxi, No. 20161ACG70012.
Institutional animal care and use committee statement: This study was approved by the Animal Research Committee, Central South University, Hunan, China.
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: Raw sequencing data are available from the corresponding author at lgtmhu@163.com. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guideline.
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/
Corresponding author: Guang-Tao Lei, MD, Chief Doctor, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, 1st Minde Road, Nanchang 330006, Jiangxi Province, China. lgtmhu@163.com
Telephone: +86-13257090106 Fax: +86-791-86311676
Received: December 17, 2018
Peer-review started: December 17, 2018
First decision: January 18, 2019
Revised: January 25, 2019
Accepted: January 28, 2019
Article in press: January 29, 2019
Published online: February 28, 2019
Processing time: 72 Days and 21.3 Hours
Abstract
BACKGROUND

Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity, but the mechanisms underlying these effects are unclear.

AIM

To investigate the effects of procyanidin B2 (PB2) on non-alcoholic fatty liver disease and to explore the possible mechanism.

METHODS

Thirty male New Zealand white rabbits were randomized into three groups. All of them were fed either a high-fat-cholesterol diet (HCD) or chow diet. HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk. Body weight and food intake were evaluated once a week. Serum biomarkers, such as total cholesterols, triglycerides, and aspartate transaminase, were detected. All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections. Moreover, several lipogenic genes and gut microbiota (by 16S rRNA sequencing) were investigated to explore the possible mechanism.

RESULTS

The HCD group had higher body weight, liver index, serum lipid profile, insulin resistance, serum glucose, and hepatic steatosis compared to the CHOW group. PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver. PB2 also ameliorated low-grade inflammation, which was reflected by serum lipopolysaccharides and improved insulin resistance. In rabbit liver, PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase, compared to the HCD group. Moreover, HCD led to a decrease of Bacteroidetes in gut microbiota. PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.

CONCLUSION

Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.

Keywords: Procyanidin; Rabbit; Non-alcoholic fatty liver disease; Gut microbiota; 16S rRNA

Core tip: Procyanidins are widely recognized for their excellent antioxidant properties and fewer side effects compared to other drugs. In the past, the mechanism of procyanidin to improve insulin resistance mainly focused on the antioxidant effect. The effect of procyanidin on non-alcoholic fatty liver disease is not clear. We found that procyanidin can reduce fatty liver by remodeling intestinal flora, decreasing endotoxemia, and down-regulating fatty acid synthesis genes. Our results open a new chapter in the mechanism of action of plant compounds and suggest a safer method for the treatment of non-alcoholic fatty liver disease.