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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 22, 2022 |
| Title |
Cardiac lipidomic profiling and mechanistic exploration by transcriptome in murine model of dilated cardiomyopathy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dilated cardiomyopathy (DCM) and heart failure are associated with mitochondrial dysfunction and dysregulated lipid metabolism. Recent studies have implicated a pivotal role of Hippo pathway activation in the development of DCM with profound metabolic remodelling. However, alterations in the cardiac lipid profile and responsible molecular mechanisms, including upregulated galectin-3, remain unclear in the setting of DCM. Mice with DCM induced by Hippo pathway activation (Mst1 gene overexpression alone or with galectin-3 gene deletion) were studied by lipidomic profiling, transcriptomic profiling and immunoblotting for mRNA and protein expression. Profound alterations in cardiac lipid classes were observed, notably elevated sphingolipids, reduced triacylglycerol (TG) and ether lipids, alterations in phospholipid species, elevated lysophosphatidylcholine, and a profound reduction in mitochondria-specific cardiolipin and coenzyme Q10. Relative to adult mice with advanced DCM, reduced TG content was evident but sphingolipid accumulation was absent in young mice at early phase of DCM. Mechanistically, the lipidomic profile in DCM heart was in consistent with dysregulated expression of specific gene sets for biosynthesis of ceramides or TG, TG storage/hydrolysis, mitochondrial lipid metabolism, peroxisome biogenesis, and suppressed PPAR-alpha signaling. Furthermore, galectin-3 gene deletion resulted in changes in some lipid classes and numerous lipid species in settings of healthy and DCM. Multiple alterations in cardiac lipids were identified by lipidomics in a mouse model of DCM due to activation of the Hippo pathway. By employing transcriptome and galectin-3 gene deletion, we revealed underlying mechanisms for lipid abnormalities involving upregulated galectin-3, downregulated expression of specific gene sets of lipid metabolism, and attenuated PPAR-alpha signaling.
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| Overall design |
C57BL6 mice with DCM induced by Hippo pathway activation were studied by lipidomic profiling, transcriptomic profiling and immunoblotting for mRNA and protein expression and comparisons were made to control mice. The files included in this submission relate to 3 week old mice. Adult mice (15 week old) were described in a previous submission (GSE106201).
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| Contributor(s) |
Wu W, Huynh K, Ziemann M, Duong T, Du J, She G, Zhao W, Deng X, J.Meikle P, Du X |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Sep 19, 2022 |
| Last update date |
Sep 22, 2022 |
| Contact name |
Mark D Ziemann |
| E-mail(s) |
mark.ziemann@gmail.com
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| Organization name |
Deakin University
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| Department |
Life and Environmental Sciences
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| Street address |
75 Pigdons rd
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| City |
Waurn Ponds |
| State/province |
VIC |
| ZIP/Postal code |
3216 |
| Country |
Australia |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA882094 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213707_count_matrix.tsv.gz |
726.4 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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