| Exposure to Resveratrol triggers Pharmacological Correction of Fatty Acid Utilization in Human Fatty Acid Oxidation-deficient Fibroblasts. | |
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MedLine Citation:
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PMID: 21378393 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Carnitine Palmitoyl Transferase 2 (CPT2) and Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) deficiencies are among the most common inborn mitochondrial fatty acid ß-oxidation (FAO) disorders. Despite advances in their clinical and molecular characterizations, few therapeutic approaches exist for these diseases. Resveratrol (RSV) is a natural polyphenol extensively studied for its potential health benefits. Indeed, it is presently thought that resveratrol could delay the onset of some cancers, and have protective effects against common ageing disorders like type II diabetes, cardiovascular, or neurodegenerative diseases. Here, we show that exposure to RSV induces a dose-and time-dependant increase in FAO flux in human fibroblasts, and can restore normal FAO capacities in a panel of patients' fibroblasts with the mild forms (harboring various genotypes) of CPT2 or VLCAD deficiency. The correction of FAO flux correlated with a marked increase in mutant CPT2 or VLCAD protein level, in cells treated by RSV. Inhibition of SIRT1 by Sirtinol and the use of PGC-1α SiRNAs demonstrate that the RSV-induced stimulation of FAO requires the presence of PGC-1α and SIRT1. These results show for the first time that RSV markedly induces mitochondrial FAO capacities in human fibroblasts, and provides the initial proof-of-concept that RSV might be efficient for correction of inherited FAO disorders. |
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Authors:
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Jean Bastin; Alexandra Lopes-Costa; Fatima Djouadi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-5 |
Journal Detail:
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Title: Human molecular genetics Volume: - ISSN: 1460-2083 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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INSERM U747, Université Paris Descartes, Paris, France. |
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