title: Aging and obesity induce distinct gene expression adaptation in the liver of C57BL/6J mice.
abstract: BACKGROUND
  Aging and obesity induce complex transcriptomic changes in the liver, promoting the development of insulin resistance and type 2 diabetes. In spite of an increasing amount of studies on the role of aging and nutrient excess in metabolic disorders, the specific molecular events leading to insulin resistance are still poorly understood.
  
  
  METHODS
  This study presents a comparative analysis of hepatic gene expression profiles between young adult C57BL/6J mice fed with a low- or a high-fat diet for 1 and 12 months. We evaluated the expression of a defined set of genes implicated in glucose and lipid metabolism as well as key nuclear receptors and their target genes, IGF1 signaling and clock genes.
  
  
  RESULTS
  Aging and short-term high-fat consumption induced insulin resistance, albeit through two distinct processes. Hepatic gene expression changes were more pronounced in the context of aging. We further analyzed expression profiles together with plasma parameters by principal component analysis with regard to diet condition.
  
  
  CONCLUSIONS
  Our results suggest that in the liver of C57BL/6J mice, the molecular mechanisms underlying high-fat feeding or aging which mediated insulin resistance were not identical.
authors.affiliation: Metabolic Diseases Research Institut de Recherches Servier, Suresnes, France.
authors.forename: F
authors.initials: F
authors.lastname: Capel
authors.forename: M H
authors.initials: MH
authors.lastname: Delmotte
authors.forename: M
authors.initials: M
authors.lastname: Brun
authors.forename: M
authors.initials: M
authors.lastname: Lonchampt
authors.forename: B
authors.initials: B
authors.lastname: De Fanti
authors.forename: L
authors.initials: L
authors.lastname: Xuereb
authors.forename: L
authors.initials: L
authors.lastname: Baschet
authors.forename: G
authors.initials: G
authors.lastname: Rolland
authors.forename: J P
authors.initials: JP
authors.lastname: Galizzi
authors.forename: B
authors.initials: B
authors.lastname: Lockhart
authors.forename: A
authors.initials: A
authors.lastname: Ktorza
authors.forename: C
authors.initials: C
authors.lastname: Dacquet
mesh_terms: D000222:Adaptation, Physiological; D000375:Aging / Q000235:genetics*; D000818:Animals; D004032:Diet; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction