Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country, Vitoria, Spain.
Mol Nutr Food Res. 2012 Oct;56(10):1559-68. doi: 10.1002/mnfr.201100772. Epub 2012 Sep 4.
Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue.
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.
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.
由于白藜芦醇的生物利用度较低，因此确定其代谢产物是否具有任何有益作用是一个有趣的问题。
3T3-L1 成熟前脂肪细胞在分化的第 0 天至第 8 天以及第 12 天的成熟脂肪细胞中处理 24 小时，用 1、10 或 25μM 的白藜芦醇或其代谢物处理。通过分光光度法评估三酰基甘油，通过实时 RT-PCR 评估基因表达。在 25μM 时，白藜芦醇、反式白藜芦醇-4'-O-葡萄糖苷和反式白藜芦醇-3-O-硫酸盐可降低成熟前脂肪细胞中的三酰基甘油含量。在成熟的脂肪细胞中，白藜芦醇及其葡萄糖苷代谢物（硫酸盐代谢物除外）降低了三酰基甘油含量，尽管白藜芦醇比它们更有效。白藜芦醇和三种代谢物降低了 C/EBPβ mRNA 水平。反式白藜芦醇-3-O-硫酸盐还降低了 C/EBP-α、过氧化物酶体增殖物激活受体γ（PPAR-γ）和脂蛋白脂肪酶（LPL）的表达。在成熟的脂肪细胞中，白藜芦醇增加了 ATGL、CPT-1、脱乙酰基酶 SIRT-1 和 PGC1-α 的表达。反式白藜芦醇-3-O-葡萄糖苷降低了 FASN 的 mRNA 水平，增加了 SIRT-1 的水平。反式白藜芦醇-4'-O-葡萄糖苷增加了 HSL 和 SIRT-1 的 mRNA 水平。反式白藜芦醇-3-O-硫酸盐没有改变基因表达。
本研究首次表明（i）代谢物在成熟前脂肪细胞中的去脂作用，以及（ii）葡萄糖苷代谢物在成熟脂肪细胞中的去脂作用。这表明白藜芦醇及其代谢物可能都参与了这种多酚的抗肥胖作用。
