An 8-week high-fat diet induces obesity and insulin resistance with small changes in the muscle transcriptome of C57BL/6J mice.
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.
de Wilde
Janneke
J
Nutrigenomics Consortium, Top Institute Food and Nutrition, Wageningen University, Wageningen, The Netherlands. j.dewilde@hb.unimaas.nl
Smit
Egbert
E
Mohren
Ronny
R
Boekschoten
Mark V
MV
de Groot
Philip
P
van den Berg
Sjoerd A A
SA
Bijland
Silvia
S
Voshol
Peter J
PJ
van Dijk
Ko Willems
KW
de Wit
Nicole W J
NW
Bunschoten
Annelies
A
Schaart
Gert
G
Hulshof
Martijn F M
MF
Mariman
Edwin C M
EC
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
D052242:Adiponectin; D004041:Dietary Fats; D012313:RNA; D005947:Glucose