title: Hepatic gene expression profiling in Nrf2 knockout mice after long-term high-fat diet-induced obesity.
abstract: BACKGROUND
  The transcription factor NFE2-related factor 2 (Nrf2) is a central regulator of antioxidant and detoxification gene expression in response to electrophilic or oxidative stress. Nrf2 has recently been shown to cross-talk with metabolic pathways, and its gene deletion protected mice from high-fat-diet-(HFD-) induced obesity and insulin resistance. This study aimed to identify potential Nrf2-regulated genes of metabolic interest by comparing gene expression profiles of livers of wild-type (WT) versus Nrf2 knockout (Nrf2-KO) mice after a long-term HFD.
  
  
  METHODS
  WT and Nrf2-KO mice were fed an HFD for 180 days; total RNA was prepared from liver and used for microarray analysis and quantitative real-time RT-PCR (qRT-PCR).
  
  
  RESULTS
  The microarray analysis identified 601 genes that were differentially expressed between WT and Nrf2-KO mice after long-term HFD. Selected genes, including ones known to be involved in metabolic regulation, were prioritized for verification by qRT-PCR: Cyp7a1 and Fabp5 were significantly overexpressed in Nrf2-KO mice; in contrast, Car, Cyp2b10, Lipocalin 13, Aquaporin 8, Cbr3, Me1, and Nqo1 were significantly underexpressed in Nrf2-KO mice.
  
  
  CONCLUSIONS
  Transcriptome profiling after HFD-induced obesity confirms that Nrf2 is implicated in liver metabolic gene networks. The specific genes identified here may provide insights into Nrf2-dependent mechanisms of metabolic regulation.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
authors.forename: Dionysios V
authors.initials: DV
authors.lastname: Chartoumpekis
authors.forename: Panos G
authors.initials: PG
authors.lastname: Ziros
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zaravinos
authors.forename: Ralitsa P
authors.initials: RP
authors.lastname: Iskrenova
authors.forename: Agathoklis I
authors.initials: AI
authors.lastname: Psyrogiannis
authors.forename: Venetsana E
authors.initials: VE
authors.lastname: Kyriazopoulou
authors.forename: Gerasimos P
authors.initials: GP
authors.lastname: Sykiotis
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Habeos
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger