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| Status |
Public on May 06, 2019 |
| Title |
The white adipose tissue transcriptional response to withdrawal of vitamin B3 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Distinct markers for early, mild vitamin B3 deficiency are lacking. To identify these, we examined the molecular responses of white adipose tissue to vitamin B3 withdrawal. We performed a dietary intervention in male C57Bl/6JRcc mice. A diet with a low but adequate level of tryptophan without nicotinamide riboside (NR) was compared to the same diet with NR at the recommended vitamin B3 (30 mg NR per kg diet). Physiological and circulating parameters were determined and global transcriptomics, qRT-PCR and histology of epididymal white adipose tissue (eWAT) were done. We observed a decreased insulin sensitivity and a shift from carbohydrate to fatty acid oxidation. This was consistent with molecular changes in eWAT, where we observed an altered MEK/ERK signalling, a lowering of glucose utilization markers and an increase in makers of fatty acid catabolism, which may be related to the consistent reduction of mitochondrial OXPHOS Complex I (mRNAs and protein). The synthesis pathway of tetrahydropteridine (BH4), an essential cofactor for neurotransmitter synthesis, was found to be increased. Based on our results, we propose the technically validated downregulation of Anp32a, Tnk2 and the upregulation of Mapk1, Map2k1, Mthfs, Mthfsl and Qdpr as a WAT transcriptional signature marker for mild vitamin B3 deficiency.
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| Overall design |
The C57BL/6JRcc male mice (8 or 9 weeks old) were individually housed (12h light–dark cycle, 23±1°C, 55±15% humidity), with ad libitum access to feed and water. A semi-synthetic diet (40% energy from fat, 19% energy from protein, 41% energy from carbohydrates) was designed to contain a low, but sufficient amount of tryptophan (calculated 0.115% L-tryptophan) and either 0 or 30 mg nicotinamide riboside (NR) per kg diet as vitamin B3 (referred to as No NR and Ctrl NR, respectively). Mice were accustomed to this diet (Ctrl NR) for two weeks. Subsequently, mice were stratified into 2 experimental groups on mean body weight (n=12/group) and received the Ctrl NR or No NR diet for 18 weeks. Mice were provided with a limited amount of diet (with 0.8 gram of fresh experimental diet) at start of dark phase to have them fasted at end of dark phase; they were subsequently refed at start of light phase with 1.8 gram of diet for four hours and then sacrificed by decapitation.
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| Contributor(s) |
Shi W, de Boer V, van Schothorst EM, van der Stelt I, Keijer J |
| Citation(s) |
30990964 |
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| Submission date |
Jul 01, 2018 |
| Last update date |
May 08, 2019 |
| 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 (24)
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| Relations |
| BioProject |
PRJNA478790 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE116483_RAW.tar |
152.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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