We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD<sup>+</sup> in medium-chain acyl-CoA dehydrogenase knockout mice.
- Authors
Martines, Anne-Claire M. F.; Gerding, Albert; Stolle, Sarah; Vieira-Lara, Marcel A.; Wolters, Justina C.; Jurdzinski, Angelika; Bongiovanni, Laura; de Bruin, Alain; van der Vlies, Pieter; van der Vries, Gerben; Bloks, Vincent W.; Derks, Terry G. J.; Reijngoud, Dirk-Jan; Bakker, Barbara M.
- Abstract
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.
- Subjects
TRANSCRIPTOMES; COENZYME A; DEHYDROGENASES; ENZYME deficiency; LABORATORY mice
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-019-50758-0