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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 17, 2015 |
| Title |
Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.-Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., and Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux.
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| Overall design |
Control C57BL/6J wildtype male mice, aged 12 weeks, are compared to UCP1 transgene littermates fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 12 weeks . At the end, mice were sacrificed, gastrocnemius skeletal muscle was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays. In total, 6 arrays of individual WT and 7 arrays of individual UCP1-TG samples were normalized, together with samples from the complete SUPERSERIES.
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| Contributor(s) |
Ost M, van Schothorst E, Keipert S, van der Stelt I, Klaus S, Keijer J |
| Citation(s) |
25491309 |
| Submission date |
Apr 11, 2013 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Evert M. van Schothorst |
| E-mail(s) |
evert.vanschothorst@wur.nl
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| Organization name |
Wageningen University
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| Lab |
Human and Animal Physiology
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| Street address |
De Elst 1
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| City |
Wageningen |
| ZIP/Postal code |
6708 WD |
| Country |
Netherlands |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (13)
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| GSM1121376 |
control WT, LFD, replicate 4 |
| GSM1121377 |
control WT, LFD, replicate 5 |
| GSM1121378 |
control WT, LFD, replicate 6 |
| GSM1121379 |
UCP1 Transgene sk.muscle, LFD, replicate 1 |
| GSM1121380 |
UCP1 Transgene sk.muscle, LFD, replicate 2 |
| GSM1121381 |
UCP1 Transgene sk.muscle, LFD, replicate 3 |
| GSM1121382 |
UCP1 Transgene sk.muscle, LFD, replicate 4 |
| GSM1121383 |
UCP1 Transgene sk.muscle, LFD, replicate 5 |
| GSM1121384 |
UCP1 Transgene sk.muscle, LFD, replicate 6 |
| GSM1121385 |
UCP1 Transgene sk.muscle, LFD, replicate 7 |
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| This SubSeries is part of SuperSeries: |
| GSE45993 |
The effects of ectopic UCP1 expression on gene expression in skeletal muscle |
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| Relations |
| BioProject |
PRJNA196841 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45991_RAW.tar |
275.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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