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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tucci, Sara Behringer, Sidney Spiekerkoetter, Ute |
| Description | Country affiliation: Germany Author Affiliation: Tucci S ( Department of General Paediatrics, Centre for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.); Behringer S ( Department of General Paediatrics, Centre for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.); Spiekerkoetter U ( Department of General Paediatrics, Centre for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.) |
| Abstract | An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal ß-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal ß-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. |
| File Format | HTM / HTML |
| ISSN | 1742464X |
| Issue Number | 21 |
| Volume Number | 282 |
| e-ISSN | 17424658 |
| Journal | FEBS Journal |
| Language | English |
| Publisher | Wiley (on behalf of the Federation of European Biochemical Societies) |
| Publisher Date | 2015-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Acyl-coa Dehydrogenase, Long-chain Deficiency Fatty Acids Administration & Dosage Biosynthesis Lipid Metabolism, Inborn Errors Diet Therapy Metabolism Mitochondrial Diseases Muscular Diseases Genetics Animals Dietary Fats Disease Models, Animal Chemistry Female Liver Male Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Myocardium Oxidation-reduction Peroxisomes Triglycerides Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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