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Scripta Scientifica Pharmaceutica

UNDERSTANDING THE ANTI-OBESITY EFFECTS OF RESVERATROL: PHASE-II CONJUGATES VS GUT MICROBIOTA METABOLITES

M. Suárez, A. Ardid-Ruiz, M. Ibars, P. Mena, D. del Rio, C. Bladé, G. Aragonès

Abstract

Introduction: Resveratrol (RSV) has been recently reported as preventing obesity. However, as RSV is quickly metabolized by both phase-II enzymes and gut microbiota, it is necessary to simultaneously analyze its metabolites in plasma in order to understand the mechanism of action of this compound.

Aim: The aim of this study was to identify which blood RSV metabolites could be potentially involved in the anti-obesity effects of RSV.

Materials and Methods: Five groups (n=6) of Wistar rats were fed a standard (STD) or cafeteria (CAF) diet for 12 weeks and were orally treated with 0, 50, 100 and 200 mg/kg/day of RSV during the last three weeks of the study period. At the end of the treatment, RSV metabolites were quantified in plasma by liquid chromatography-tandem mass spectrometry and body fat content was assessed by RMN. MetaboAnalyst was used to perform multivariant statistical analyses.

Results: The consumption of RSV at doses of 50 and 100 mg/kg/day did not prevent body weight gain in our experimental conditions, and only the dose of 200 mg/kg/day reduced obesity as indicated by significant decreases in body fat mass and circulating leptin levels. According to different metabolic variables, the PCA and PLS-DA analyses showed that animals treated at dose of 200 mg/kg/day were the closest to the group of lean animals. Notably, the observed separations were significantly related to the presence of higher concentrations of microbiota metabolites at dose of 200 mg/kg/day. In fact, only microbiota metabolites (dihydroresveratrol forms), but not phase-II conjugates, showed a significant dose-response pattern. Finally, the animal’s weight was significantly correlated to the plasmatic concentrations of dihydroresveratrol metabolites.

Conclusion: The RSV metabolites derived from gut microbiota could explain, at least partially, the contribution of high doses of RSV to reduce the metabolic disorders associated with obesity.

Acknowledgements: The research was financially supported by grant AGL2013-40707-R from the Spanish Ministry of Economy and Competitiveness and ERDF fund


Keywords

Resveratrol, cafeteria diet, obesity, metabolites, multivariant




DOI: http://dx.doi.org/10.14748/ssp.v4i1.3976

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About The Authors

M. Suárez

A. Ardid-Ruiz

M. Ibars

P. Mena

D. del Rio

C. Bladé

G. Aragonès

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