Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Straße 6, 24118, Kiel, Germany.
Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, Leipziger Straße 123, 36037, Fulda, Germany.
Sci Rep. 2019 Mar 14;9(1):4445. doi: 10.1038/s41598-019-41050-2.
Resveratrol as well as caloric restriction were shown to extend lifespan in some model organisms and may possibly delay onset of ageing-related diseases in humans. Yet, resveratrol supplementation does not always extend lifespan of animal models or improve health status of humans. Because of interindividual differences in human microbiota, resveratrol metabolite production in the gut differs. While some individuals produce lunularin and dihydroresveratrol in their gut, others produce dihydroresveratrol only. Therefore, we addressed the question whether these metabolites differ in their biological impact on ageing and intraperitoneally injected 13-month-old C57BL/6JRj mice on an ad-libitum (AL) HFD with resveratrol, dihydroresveratrol or lunularin (24 mg/kg bodyweight; 3 times/week). Compared to mice injected with vehicle (AL-control), resveratrol and dihydroresveratrol did not change bodyweight and had no impact on insulin or glucose levels while lunularin slightly reduced feed intake and bodyweight gain. CR-mice showed lowered cholesterol, insulin and leptin levels, elevated adiponectin and phosphorylated AMPK levels in liver as well as increased transcription of Pck1 and Pgc1α when compared to the AL-control. In contrast, injections with the test substances did not change these parameters. We therefore conclude that in our model, resveratrol, lunularin and dihydroresveratrol did not act as CR mimetics.
白藜芦醇和热量限制已被证明可以延长某些模式生物的寿命，并可能延缓人类衰老相关疾病的发病。然而，白藜芦醇的补充并不总是能延长动物模型的寿命或改善人类的健康状况。由于人类微生物群存在个体差异，肠道中白藜芦醇的代谢产物也不同。一些人在肠道中产生白藜芦醇苷和二氢白藜芦醇，而另一些人则只产生二氢白藜芦醇。因此，我们提出了一个问题，即这些代谢物在对衰老的生物学影响方面是否存在差异，并给 13 个月大的 C57BL/6JRj 雄性小鼠（在自由饮食 AL-HFD 上）腹膜内注射白藜芦醇、二氢白藜芦醇或白藜芦醇苷（24mg/kg 体重；每周 3 次）。与注射溶剂（AL-对照）的小鼠相比，白藜芦醇和二氢白藜芦醇没有改变体重，对胰岛素或葡萄糖水平没有影响，而白藜芦醇苷则略微减少了采食量和体重增加。与 AL-对照相比，CR 组的小鼠胆固醇、胰岛素和瘦素水平降低，肝脏中的脂联素和磷酸化 AMPK 水平升高，Pck1 和 Pgc1α 的转录增加。相比之下，这些测试物质的注射并没有改变这些参数。因此，我们得出结论，在我们的模型中，白藜芦醇、白藜芦醇苷和二氢白藜芦醇没有作为 CR 模拟物发挥作用。
