Nuclear receptor-mediated alleviation of alcoholic fatty liver by polyphenols contained in alcoholic beverages

Ruiqing Yao; Akihito Yasuoka; Asuka Kamei; Shota Ushiama; Yoshinori Kitagawa; Tomohiro Rogi; Hiroshi Shibata; Keiko Abe; Takumi Misaka

doi:10.1371/journal.pone.0087142

Nuclear receptor-mediated alleviation of alcoholic fatty liver by polyphenols contained in alcoholic beverages

PLoS One. 2014 Feb 3;9(2):e87142. doi: 10.1371/journal.pone.0087142. eCollection 2014.

Authors

Ruiqing Yao¹, Akihito Yasuoka², Asuka Kamei³, Shota Ushiama¹, Yoshinori Kitagawa⁴, Tomohiro Rogi⁴, Hiroshi Shibata⁴, Keiko Abe⁵, Takumi Misaka¹

Affiliations

¹ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
² Department of Biological Engineering, Maebashi Institute of Technology, Maebashi-shi, Gunma, Japan ; Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki-shi, Kanagawa, Japan.
³ Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki-shi, Kanagawa, Japan.
⁴ Institute for Health Care Science, Suntory Wellness Ltd., Shimamoto-cho, Mishima-gun, Osaka, Japan.
⁵ Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan ; Kanagawa Academy of Science and Technology, Takatsu-ku, Kawasaki-shi, Kanagawa, Japan.

Abstract

To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alcoholic Beverages*
Animals
Antioxidants / pharmacology
Central Nervous System Depressants / pharmacology
Constitutive Androstane Receptor
Ellagic Acid / pharmacology
Ethanol / pharmacology
Fatty Liver, Alcoholic / genetics
Fatty Liver, Alcoholic / prevention & control*
Female
Gene Ontology
Liver / drug effects
Liver / metabolism
Metabolic Networks and Pathways / genetics
Mice
Mice, Inbred C3H
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Polyphenols / pharmacology*
Receptors, Cytoplasmic and Nuclear / deficiency*
Receptors, Cytoplasmic and Nuclear / genetics
Resveratrol
Stilbenes / pharmacology
Transcriptome / drug effects
Transcriptome / genetics

Substances

Antioxidants
Central Nervous System Depressants
Constitutive Androstane Receptor
Polyphenols
Receptors, Cytoplasmic and Nuclear
Stilbenes
Ellagic Acid
Ethanol
Resveratrol

Associated data

GEO/GSE52644

Grants and funding

This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.M., to K.A.), and by the Funding Program for Next-Generation World-Leading Researchers from the Japan Society for the Promotion of Science (to T.M.) and an Iijima Shokuseikatu (to A.Y.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.