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Tissue-Specific Strategies of the Very-Long Chain Acyl-CoA Dehydrogenase-Deficient (VLCAD−/−) Mouse to Compensate a Defective Fatty Acid β-Oxidation
| Content Provider | Semantic Scholar |
|---|---|
| Author | Tucci, Sara Herebian, Diran Sturm, Marga Seibt, Annette Spiekerkoetter, Ute |
| Copyright Year | 2012 |
| Abstract | Very long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency is the most common long-chain fatty acid oxidation disorder presenting with heterogeneous phenotypes. Similar to many patients with VLCADD, VLCAD-deficient mice (VLCAD(-/-)) remain asymptomatic over a long period of time. In order to identify the involved compensatory mechanisms, wild-type and VLCAD(-/-) mice were fed one year either with a normal diet or with a diet in which medium-chain triglycerides (MCT) replaced long-chain triglycerides, as approved intervention in VLCADD. The expression of the mitochondrial long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was quantified at mRNA and protein level in heart, liver and skeletal muscle. The oxidation capacity of the different tissues was measured by LC-MS/MS using acyl-CoA substrates with a chain length of 8 to 20 carbons. Moreover, in white skeletal muscle the role of glycolysis and concomitant muscle fibre adaptation was investigated. In one year old VLCAD(-/-) mice MCAD and LCAD play an important role in order to compensate deficiency of VLCAD especially in the heart and in the liver. However, the white gastrocnemius muscle develops alternative compensatory mechanism based on a different substrate selection and increased glucose oxidation. Finally, the application of an MCT diet over one year has no effects on LCAD or MCAD expression. MCT results in the VLCAD(-/-) mice only in a very modest improvement of medium-chain acyl-CoA oxidation capacity restricted to cardiac tissue. In conclusion, VLCAD(-/-) mice develop tissue-specific strategies to compensate deficiency of VLCAD either by induction of other mitochondrial acyl-CoA dehydrogenases or by enhancement of glucose oxidation. In the muscle, there is evidence of a muscle fibre type adaptation with a predominance of glycolytic muscle fibres. Dietary modification as represented by an MCT-diet does not improve these strategies long-term. |
| Starting Page | 16321 |
| Ending Page | 16331 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045429&type=printable |
| PubMed reference number | 23024820v1 |
| Volume Number | 7 |
| Journal | PloS one |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acclimatization Acyl Coenzyme A Body tissue Carbon Deficiency of butyryl-CoA dehydrogenase Fatty Acids Genetic Heterogeneity Glucose Glycolysis Medium-chain acyl-coenzyme A dehydrogenase deficiency Muscle Fibers Myalgia Oxidoreductase Patients Phenotype Post-Translational Protein Processing Thioctic Acid Triglycerides Very long chain acyl-CoA dehydrogenase deficiency fatty acid oxidation |
| Content Type | Text |
| Resource Type | Article |
