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| Status |
Public on Sep 21, 2010 |
| Title |
Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: Physical inactivity is a risk factor for insulin resistance. We examined the effect of nine days of bed rest on basal and insulin stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy, young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene. Subjects were re-examined after four weeks of retraining. Findings: Bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after four weeks of retraining. Pathway analyses revealed significant down-regulation of 34 pathways, predominantly those of genes associated with mitochondrial function including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. Conclusions: Impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after four weeks of exercise retraining underscores the importance of maintaining a minimum of daily physical activity.
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| Overall design |
50 samples were collected (5 samples from 10 subjects) and included in this study. Ten technical repeats were also performed in this analysis
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| Contributor(s) |
Alibegovic AC, Sonne MP, Højbjerre L, Bork-Jensen J, Jacobsen S, Nilsson E, Færch K, Hiscock N, Mortensen B, Friedrichsen M, Stallknecht B, Dela F, Vaag A |
| Citation(s) |
20739510 |
| Submission date |
Sep 20, 2010 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Natalie Hiscock |
| E-mail(s) |
natalie.hiscock@unilever.com
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| Organization name |
Unilever R&D
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| Street address |
Colworth House
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| City |
Sharnbrook |
| ZIP/Postal code |
MK44 1LQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA132951 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24215_RAW.tar |
461.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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