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| Status |
Public on Jun 18, 2012 |
| Title |
Altered de novo lipogenesis contributes to low adipose stores in cystic fibrosis mice. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Cystic fibrosis (CF) mouse models exhibit exocrine pancreatic function yet do not develop adipose stores to the levels of non-CF mice. CF mice homozygous for the Cftr mutation (F508del) at 3 weeks (post-weaning) and 6 weeks (young adult) of age had markedly less adipose tissue than non-CF mice. Both 3- and 6-week old mice had dietary lipid absorption and fecal lipid excretion comparable to non-CF controls. Fractional hepatic de novo synthesis of palmitate and stearate (de novo lipogenesis, DNL) as determined by deuterium incorporation was reduced in CF mice. At 3 weeks of age, F508del mice had significantly decreased DNL of palmitate and stearate, by 83% and 80%, respectively. By 6 weeks of age, DNL rates in non-CF mice remained unchanged as compared to 3-week old mice, while DNL rates of F508del mice were still reduced, by 33% and 40%, respectively. Adipose tissue fatty acid profiles were comparable in CF and non-CF mice, indicating that adipose differences are quantitative, not qualitative. A correspondingly lower content of deuterium-labeled fatty acids was found in CF adipose tissue, consistent with reduced deposition of newly made hepatic triglycerides and/or decreased adipose tissue lipogenesis. Hepatic transcriptome analysis revealed lower mRNA expression from several genes involved in fatty acid biosynthesis, suggesting down-regulation of several enzymes in fatty acids synthesis as a mechanism for the reduced lipogenesis. These novel data provide a model for altered fat and fatty acid metabolism in CF, independent of malabsorption, and may partly explain the inability of pancreatic enzyme replacement therapy to completely restore normal body mass to CF patients
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| Overall design |
∆F508 CF mice and its WT littermates (3-weeks old females, C57BL/6J) were examined. RNA extracted from snapped-frozen livers, 4 replicates per genotype.
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| Contributor(s) |
Perez A, Drumm ML |
| Citation(s) |
22679004 |
| Submission date |
Oct 28, 2011 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Aura Perez |
| E-mail(s) |
aura.perez@case.edu
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| Phone |
216-368-6894
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| Organization name |
CWRU
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| Department |
Pediatrics
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| Street address |
10900 Euclid Avenue
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| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44106-4948 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA149291 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33319_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE33319_non-normalized.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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