Back to Search
Start Over
Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts
- Source :
- Orphanet Journal of Rare Diseases, Orphanet Journal of Rare Diseases, BioMed Central, 2014, 9 (1), pp.79. ⟨10.1186/1750-1172-9-79⟩, Orphanet Journal of Rare Diseases, 2014, 9 (1), pp.79. ⟨10.1186/1750-1172-9-79⟩
- Publication Year :
- 2014
- Publisher :
- HAL CCSD, 2014.
-
Abstract
- International audience; Background: Inborn enzyme defects of mitochondrial fatty acid beta-oxidation (FAO) form a large group of genetic disorders associated to variable clinical presentations ranging from life-threatening pediatric manifestations up to milder late onset phenotypes, including myopathy. Very few candidate drugs have been identified in this group of disorders. Resveratrol (RSV) is a natural polyphenol with anti-oxidant and anti-inflammatory effects, recently shown to have beneficial metabolic properties in mice models. Our study explores its possible effects on FAO and mitochondrial energy metabolism in human cells, which are still very little documented.Methods: Using cells from controls and from patients with Carnitine Palmitoyl Transferase 2 (CPT2) or Very Long Chain AcylCoA Dehydrogenase (VLCAD) deficiency we characterized the metabolic effects of RSV, RSV metabolites, and other stilbenes. We also focused on analysis of RSV uptake, and on the effects of low RSV concentrations, considering the limited bioavailability of RSV in vivo.Results: Time course of RSV accumulation in fibroblasts over 48 h of treatment were consistent with the resulting stimulation or correction of FAO capacities. At 48 h, half maximal and maximal FAO stimulations were respectively achieved for 37,5 microM (EC50) and 75 microM RSV, but we found that serum content of culture medium negatively modulated RSV uptake and FAO induction. Indeed, decreasing serum from 12% to 3% led to shift EC50 from 37,5 to 13 microM, and a 2.6-3.6-fold FAO stimulation was reached with 20 microM RSV at 3% serum, that was absent at 12% serum. Two other stilbenes often found associated with RSV, i.e. cis- RSV and piceid, also triggered significant FAO up-regulation. Resveratrol glucuro- or sulfo- conjugates had modest or no effects. In contrast, dihydro-RSV, one of the most abundant circulating RSV metabolites in human significantly stimulated FAO (1.3-2.3-fold).Conclusions: This study provides the first compared data on mitochondrial effects of resveratrol, its metabolites, and other natural compounds of the stilbene family in human cells. The results clearly indicate that several of these compounds can improve mitochondrial FAO capacities in human FAO-deficient cells.
- Subjects :
- [SDV]Life Sciences [q-bio]
Blotting, Western
Stimulation
Mitochondrion
Resveratrol
Biology
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Stilbenes
medicine
Humans
Genetics(clinical)
Pharmacology (medical)
Carnitine
Patient fibroblasts
Genetics (clinical)
030304 developmental biology
Piceid
EC50
Medicine(all)
chemistry.chemical_classification
0303 health sciences
Research
Fatty Acids
food and beverages
Mitochondrial FAO defects
Pharmacological therapy
General Medicine
Fibroblasts
Mitochondria
3. Good health
[SDV] Life Sciences [q-bio]
Enzyme
chemistry
Oxidation-Reduction
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17501172
- Database :
- OpenAIRE
- Journal :
- Orphanet Journal of Rare Diseases, Orphanet Journal of Rare Diseases, BioMed Central, 2014, 9 (1), pp.79. ⟨10.1186/1750-1172-9-79⟩, Orphanet Journal of Rare Diseases, 2014, 9 (1), pp.79. ⟨10.1186/1750-1172-9-79⟩
- Accession number :
- edsair.doi.dedup.....c43807df61e4f70c6de44b1b00fc1094