Skip to Main content Skip to Navigation
Journal articles

Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [43 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02896233
Contributor : Fatima Djouadi <>
Submitted on : Friday, July 10, 2020 - 1:31:04 PM
Last modification on : Wednesday, August 19, 2020 - 11:19:12 AM

File

Orphanet J. of rare Diseases 2...
Publisher files allowed on an open archive

Identifiers

Citation

Virginie Aires, Dominique Delmas, Carole Le Bachelier, Norbert Latruffe, Dimitri Schlemmer, et al.. Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts. Orphanet Journal of Rare Diseases, BioMed Central, 2014, 9 (1), pp.79. ⟨10.1186/1750-1172-9-79⟩. ⟨inserm-02896233⟩

Share

Metrics

Record views

25

Files downloads

74