Role of sulfotransferases in resveratrol metabolism in human adipocytes

N. Gheldof, S. Moco, C. Chabert, T. Teav, D. Barron, J. Hager

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimScope: Polyphenols such as resveratrol received interest for their wide-ranging biological benefits, including anti-obesity potential, mimicking effects of caloric restriction with reduced body fat and increased energy expenditure. However, resveratrol is rapidly metabolized, and it is not completely understood which form of resveratrol is responsible for the effects observed within target cells such as adipocytes. Also the role of metabolizing enzymes has not been investigated before. Methods and results: Resveratrol metabolism was evaluated in human adipocytes by UHPLC-MS at low physiological doses. Resveratrol was found to rapidly metabolize into its sulfated form, while resveratrol glucuronides were undetectable. Only resveratrol, but not its sulfated nor glucuronidated forms had an antilipolytic effect on adipocytes. The metabolizing enzyme responsible for sulfation of polyphenols is SULT1A1, and was found to be upregulated upon adipocyte differentiation. Knocking down SULT1A1 in adipocytes led to decreased resveratrol sulfate and increased resveratrol intra- and extracellularly. This lower SULT1A1 activity resulted in an increased antilipolytic effect of resveratrol on adipocytes, as demonstrated by lower glycerol accumulation, which could be attributed to lower activity of the lipolytic protein, perilipin. Conclusion: Sulfotransferase activity modulates metabolism of resveratrol in adipocytes with potential consequences on bioavailability and thus metabolic action of this polyphenol.
Original languageEnglish
Article number1700020
JournalMolecular Nutrition and Food Research
Volume61
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017
Externally publishedYes

Funding

N.G. and J.H. conceived the study with contributions from D.B. and S.M. N.G. coordinated the study and wrote the paper with contributions from S.M. and C.C. C.C. designed, performed, and analyzed the Western blots, knockdown and lipolysis experiments. NG designed, performed and analyzed the gene expression and Western blot experiments on p21 expression. S.M. designed and developed the LC-MS method and associated metabolite extraction. T.T. performed the metabolite extractions with help of C.C., N.G., and S.M. S.M. and T.T. carried out the LC-MS measurements and analyses. We would like to thank M. Deak and R. Hunter for technical help with the SULT1A1 enzymatic activity assays. S.M. is a participant of the EU funded COST Action FA1403 POSITIVe (interindividual variation in response to consumption of plant food bioactives and determinants involved).

FundersFunder number
C.C.
C.C. C.C.
COST Action FA1403 POSITIVe
European Commission
Western University

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