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| Status |
Public on Mar 08, 2019 |
| Title |
Effect of Nudt7 overexpression on the global transcriptome of mouse liver in the fasted state |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
RNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism.
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| Overall design |
Liver mRNA profiles of 4 mice injected with adeno-associated virus to overexpress Nudt7 and 4 mice injected with adeno-associated virus to overexpress GFP (control) were generated by RNAseq using Illumina HiSeq1500
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| Contributor(s) |
Leonardi R, Infante AM |
| Citation(s) |
30846528 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R35 GM119528 |
Changes in coenzyme A levels are a key mechanism regulating metabolic pathways |
WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION |
Roberta Leonardi |
| F31 GM126838 |
Importance of Peroxisomal Coenzyme A Degradation in Glucose Metabolism |
WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION |
Stephanie A Shumar |
| U54 GM104942 |
West Virginia Clinical and Translational Science Institute: Improving Health through Partnerships and Transformative Research |
WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION |
Sally Lynn Hodder |
| P20 GM103434 |
Genomics Core |
MARSHALL UNIVERSITY RESEARCH CORPORATION |
Donald Anthony Primerano |
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| |
| Submission date |
Jan 17, 2019 |
| Last update date |
Mar 14, 2019 |
| Contact name |
Roberta Leonardi |
| E-mail(s) |
roleonardi@hsc.wvu.edu
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| Organization name |
West Virginia University
|
| Street address |
1 Medical Center Drive
|
| City |
Morgantown |
| State/province |
WV |
| ZIP/Postal code |
26501 |
| Country |
USA |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA515623 |
| SRA |
SRP179952 |
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