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Series GSE136309 Query DataSets for GSE136309
Status Public on Oct 21, 2019
Title Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary During fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse. WT and KO mice were given a high- or low-fat diet and subsequently fasted. We analyzed histology, mitochondrial function, targeted mitochondrial proteomics, and transcriptome in liver tissue. Loss of MCAD led to a decreased capacity to oxidize octanoyl-CoA. This was not compensated for by altered protein levels of the short- and long-chain isoenzymes SCAD and LCAD. In the transcriptome, we identified subtle adaptations in the expression of genes encoding enzymes catalyzing CoA- and NAD(P)(H)-involving reactions and of genes involved in detoxification mechanisms. We discuss how these processes may contribute to robustness in MCAD-KO mice and potentially also in asymptomatic human subjects with a complete loss of MCAD activity.
 
Overall design Acadm-knockout and wild-type C57BL/6J mice were kept on a low-fat control diet or a high-fat semisynthetic diet for 6 weeks and subsequently fasted for 16 hours ) or kept on the diet for these 16 hours.
 
Contributor(s) Martines A, Gerding A, Stolle S, Vieira-Lara MA, Wolters JC, Jurdzinski A, Bongiovanni L, de Bruin A, van der Vlies P, van der Vries G, Bloks VW, Derks TG, Reingoud D, Bakker BM
Citation(s) 31601874
Submission date Aug 26, 2019
Last update date Oct 21, 2019
Contact name Sarah Stolle
E-mail(s) sarah.n.stolle@gmail.com
Organization name University of Groningen
Street address Antonius Deusinglaan 1
City Groningen
ZIP/Postal code 9713 AV
Country Netherlands
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (32)
GSM4044424 KO_HFD_Fasted Rep_1 [LR01]
GSM4044425 WT_HFD_Fed Rep_1 [LR02]
GSM4044426 KO_HFD_Fasted Rep_2 [LR03]
Relations
BioProject PRJNA562153
SRA SRP219271

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE136309_Martines_Run2_expression_table.genelevel.GRCm38.v76.htseq.txt.gz 640.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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