title: Global Liver Gene Expression Analysis on a Murine Metabolic Syndrome Model Treated by Low-molecular-weight Lychee Fruit Polyphenol (Oligonol®).
abstract: OBJECTIVE
  Oligonol® (OLG) is a low-molecular-weight lychee fruit polyphenol mainly containing catechin-type monomers and oligomers of proanthocyanidins. Dietary OLG supplementation reportedly improves lipid metabolism disorder and lowers the visceral fat level in animal and human studies. Thus, we investigated the mechanism behind the protective and beneficial effects of OLG on a Western diet (WD)-induced metabolic syndrome (MetS) of a murine model.
  
  
  METHODS
  Using the C57BL/6J mouse for the MetS model, mice were divided into three groups: control (normal diet: ND), Western diet (WD) and WD + 0.5% OLG (OLG) groups. The WD group was fed a high-calorie (high fructose plus high fat) diet for 12 weeks to develop MetS. At week 12, all mice were sacrificed and the blood and liver were obtained for histological and biological examinations and RNA sequencing (RNA-Seq).
  
  
  RESULTS
  Body weight, liver weight, plasma triglycerides (TG), total cholesterol (T-Cho) and alanine aminotransferase (ATS) levels of both OLG groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was shown to be suppressed by OLG administration. Expression gene analysis in the liver of WD- versus OLG-fed mice by RNA-Seq showed that 464/45,706 genes exhibited a significant change of expression (corrected p-value <0.05, absolute value of fold change (FC) ≥2). Gene network analysis showed that genes related to hepatic steatosis, liver inflammation and tumor invasion were inactivated in the OLG group. In particular, the lipid metabolism-related genes Lpin1, Adig and Cidea were regulated by OLG administration.
  
  
  CONCLUSIONS
  OLG may function to suppress MetS and the progression of geriatric diseases in WD-fed mice by regulating the expression of lipid metabolism, inflammation and tumor-related genes in the liver.
authors.affiliation: Genome Research Center, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Uchiyama
authors.affiliation: Department of Agricultural Science, Tokyo University of Agriculture, Atsugi, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Uehara
authors.affiliation: Department of Agricultural Science, Tokyo University of Agriculture, Atsugi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Hokkaido Pharmaceutical University School of Pharamacy, Sapporo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakata
authors.affiliation: Hokkaido Pharmaceutical University School of Pharamacy, Sapporo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Hokkaido Pharmaceutical University School of Pharamacy, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mihara
authors.affiliation: Hokkaido Pharmaceutical University School of Pharamacy, Sapporo, Japan.
authors.forename: Ken-Ich
authors.initials: KI
authors.lastname: Komatsu
authors.affiliation: Amino Up Chemical Co., Ltd., Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takanari
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Hokkaido Pharmaceutical University School of Pharamacy, Sapporo, Japan wakame-k@hokuyakudai.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Wakame
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005638:Fruit; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D032125:Litchi; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D008970:Molecular Weight; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D059467:Transcriptome
chemical_list: D010636:Phenols; D010936:Plant Extracts; C514283:oligonol; D002392:Catechin
keywords: Metabolic syndrome; RNA sequencing; hepatic steatosis; inflammation; polyphenol