title: Analysis of sterol-regulatory element-binding protein 1c target genes in mouse liver during aging and high-fat diet.
abstract: BACKGROUND
  The sterol regulatory element-binding protein (SREBP) 1c contributes to the transcriptional coordination of cholesterol, fatty acid, and carbohydrate metabolisms. Alterations in these processes accelerate the progression of hepatic steatosis and insulin resistance during aging and obesity.
  
  
  METHODS
  Using an ex vivo chromatin immunoprecipitation coupled to microarray (ChIP-on-chip) technique combined with genome-wide gene expression analysis, we analyzed the transcriptomic adaptations mediated by Srebp-1c binding to gene promoters in the liver of mice fed with a low-fat diet or a high-fat diet (HFD) for either 1 or 12 months.
  
  
  RESULTS
  Aging had a higher transcriptional impact than HFD and modified the expression of genes involved in fatty acid oxidation and oxidative stress. HFD was associated with a marked induction of genes involved in lipid and cholesterol metabolism. The prolonged high-fat feeding together with the aging effects stimulates inflammatory pathways. ChIP-on-chip applied to aging and HFD analyses revealed that the binding of SREBP-1c to a series of promoters accompanied a paralleled modification of gene expression. Therefore, SREBP-1c could play a role in aging and high-fat feeding through the regulation of genes involved in lipid metabolism and inflammatory response.
  
  
  CONCLUSIONS
  This study represents an original ex vivo experiment to elucidate the molecular events involved in metabolic disorders.
authors.affiliation: Pathophysiology and Molecular Pharmacology, Institut de Recherches Servier, Croissy-sur-Seine, France. frederic.capel@clermont.inra.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Capel
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Rolland-Valognes
authors.forename: Catherine
authors.initials: C
authors.lastname: Dacquet
authors.forename: Manuel
authors.initials: M
authors.lastname: Brun
authors.forename: Michel
authors.initials: M
authors.lastname: Lonchampt
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
authors.forename: Brian
authors.initials: B
authors.lastname: Lockhart
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Galizzi
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D004041:Dietary Fats; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1