5 years ago

Role of sulfotransferases in resveratrol metabolism in human adipocytes

Role of sulfotransferases in resveratrol metabolism in human adipocytes
Sofia Moco, Jorg Hager, Christian Chabert, Tony Teav, Denis Barron, Nele Gheldof
Scope 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. At low physiological dose, resveratrol is rapidly metabolized into its sulfated form in human adipocytes. However, it is the unmetabolized form that is responsible for the metabolic effect on adipocytes such as repressed lipolysis. By knocking down the sulfotransferase enzyme responsible for sulfating resveratrol, a higher amount of resveratrol accumulated, augmenting the decreased lipolysis, mainly through decreasing perilipin activity. Therefore, difference in sulfotransferase enzyme activity needs to be considered when evaluating the bioavailability of resveratrol.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mnfr.201700020

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