Delipidating Effect of Resveratrol Metabolites in 3T3-L1 Adipocytes

Scope: Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue.

Methods And Results: 3T3-L1 maturing pre-adipocytes were treated from day 0 to day 8 of differentiation and mature adipocytes for 24 h on day 12 with 1, 10, or 25 μM of resveratrol or its metabolites. Triacylglycerols were assessed by spectrophotometry and gene expression by real time RT-PCR. Resveratrol, trans-resveratrol-4'-O-glucuronide and trans-resveratrol-3-O-sulfate reduced triacylglycerol content in maturing pre-adipocytes at 25 μM. In mature adipocytes, both resveratrol and its glucuronide metabolites, though not sulfate metabolite, reduced triacylglycerol content, although resveratrol was more effective than them. Resveratrol and the three metabolites reduced C/EBPβ mRNA levels. Trans-resveratrol-3-O-sulfate also reduced C/EBP-α, peroxisome proliferator-activated receptor γ (PPAR-γ), and lipoprotein lipase (LPL) expression. In mature adipocytes, resveratrol increased ATGL, CPT-1, deacetylase sirtuin 1 (SIRT-1), and PGC1-α expression. Trans-resveratrol-3-O-glucuronide reduced mRNA levels of FASN and increased those of SIRT-1. Trans-resveratrol-4'-O-glucuronide increased HSL and SIRT-1 mRNA levels. Trans-resveratrol-3-O-sulfate did not change gene expression.

Conclusion: The present study shows for the first time the delipidating effect of (i) resveratrol metabolites in maturing pre-adipocytes and (ii) glucuronide metabolites in mature adipocytes. This suggests that both resveratrol and resveratrol metabolites may be involved in the anti-obesity effect of this polyphenol.