title: An 8-week high-fat diet induces obesity and insulin resistance with small changes in the muscle transcriptome of C57BL/6J mice.
abstract: BACKGROUND
  Skeletal muscle is responsible for most of the insulin-stimulated glucose uptake and metabolism. Therefore, it plays an important role in the development of insulin resistance, one of the characteristics of the metabolic syndrome (MS). As the prevalence of the MS is increasing, there is an urgent need for more effective intervention strategies.
  
  
  METHODS
  C57BL/6J mice were fed an 8-week low-fat diet (10 kcal%; LFD) or high-fat diet (45 kcal%; HFD). Microarray analysis was performed by using two comparisons: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively.
  
  
  RESULTS
  Although an 8-week HFD induced obesity and impaired insulin sensitivity, HFD-responsive changes in the muscle transcriptome were relatively small (<1.3-fold). In fact, 8-weeks of aging induced more pronounced changes than an HFD. One comparison revealed the transcriptional downregulation of the mito- gen-activated protein kinase cascade, whereas both comparisons showed the upregulation of fatty acid oxidation, demonstrating that the two comparison strategies are confirmative as well as complementary.
  
  
  CONCLUSIONS
  We suggest using complementary analysis strategies in the genome-wide search for gene expression changes induced by mild interventions, such as an HFD.
authors.affiliation: Nutrigenomics Consortium, Top Institute Food and Nutrition, Wageningen University, Wageningen, The Netherlands. j.dewilde@hb.unimaas.nl
authors.forename: Janneke
authors.initials: J
authors.lastname: de Wilde
authors.forename: Egbert
authors.initials: E
authors.lastname: Smit
authors.forename: Ronny
authors.initials: R
authors.lastname: Mohren
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.forename: Philip
authors.initials: P
authors.lastname: de Groot
authors.forename: Sjoerd A A
authors.initials: SA
authors.lastname: van den Berg
authors.forename: Silvia
authors.initials: S
authors.lastname: Bijland
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.forename: Nicole W J
authors.initials: NW
authors.lastname: de Wit
authors.forename: Annelies
authors.initials: A
authors.lastname: Bunschoten
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Martijn F M
authors.initials: MF
authors.lastname: Hulshof
authors.forename: Edwin C M
authors.initials: EC
authors.lastname: Mariman
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001823:Body Composition; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000009:adverse effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D009765:Obesity / Q000139:chemically induced*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects; D015430:Weight Gain
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D012313:RNA; D005947:Glucose