Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner
Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner
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DOI：
10.3945/ajcn.2009.28435
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发表时间：
2010-07-01
影响因子：
7.1
通讯作者：
Wabitsch, Martin
中科院分区：
文献类型：
--
作者：
Fischer-Posovszky, Pamela;Kukulus, Vera;Wabitsch, Martin
背景：热量限制导致许多生物体衰老过程的延缓和寿命的延长。这种热量限制的效果可以通过白藜芦醇来模仿，白藜芦醇是葡萄和红酒中存在的天然植物产品，其被称为沉默调节蛋白1 [沉默交配型信息调节2同源物1（Sirt 1）]的有效激活剂。我们试图确定白藜芦醇对脂肪细胞生物学的影响，并阐明是否Sirt 1参与白藜芦醇介导的changes.Design：人的Adulson-Golabi-Behmel综合征前脂肪细胞和脂肪细胞被用来研究增殖，成脂分化，葡萄糖摄取，从头脂肪生成和脂肪因子分泌。利用慢病毒小发夹RNA系统构建Sirt 1缺陷型人前脂肪细胞，研究Sirt 1在白藜芦醇介导的变化中的作用。结果：白藜芦醇以Sirt 1依赖的方式抑制前脂肪细胞增殖和成脂分化。在人类脂肪细胞中，白藜芦醇刺激基础和胰岛素刺激的葡萄糖摄取。从头脂肪生成抑制与脂肪生成基因表达的下调平行。此外，白藜芦醇下调白细胞介素-6和白细胞介素-8的表达和分泌。Sirt 1只是部分负责调节白藜芦醇介导的脂肪因子secrety.Conclusions的变化：两者合计，我们的数据表明，白藜芦醇的影响脂肪组织的质量和功能的方式，可能会积极干扰肥胖相关的合并症的发展。因此，我们的研究结果开辟了新的视角，白藜芦醇诱导的细胞内途径可能是预防或治疗肥胖相关的内分泌和代谢不良反应的靶点。美国临床营养杂志2010; 92：5-15。
Background: Caloric restriction leads to retardation of the aging processes and to longer life in many organisms. This effect of caloric restriction can be mimicked by resveratrol, a natural plant product present in grapes and red wine, which is known as a potent activator of sirtuin 1 [silent mating type information regulation 2 homolog 1 (Sirt1)].Objectives: One main effect of caloric restriction in mammals is a reduction of body fat from white adipose tissue. We sought to identify the effects of resveratrol on fat cell biology and to elucidate whether Sirt1 is involved in resveratrol-mediated changes.Design: Human Simpson-Golabi-Behmel syndrome preadipocytes and adipocytes were used to study proliferation, adipogenic differentiation, glucose uptake, de novo lipogenesis, and adipokine secretion. Sirt1-deficient human preadipocytes were generated by using a lentiviral small hairpin RNA system to study the role of Sirt1 in resveratrol-mediated changes.Results: Resveratrol inhibited preadipocyte proliferation and adipogenic differentiation in a Sirt1-dependent manner. In human adipocytes, resveratrol stimulated basal and insulin-stimulated glucose uptake. De novo lipogenesis was inhibited in parallel with a down-regulation of lipogenic gene expression. Furthermore, resveratrol down-regulated the expression and secretion of interleukin-6 and interleukin-8. Sirt1 was only partially responsible for the regulation of resveratrol-mediated changes in adipokine secretion.Conclusions: Taken together, our data suggest that resveratrol influences adipose tissue mass and function in a way that may positively interfere with the development of obesity-related comorbidities. Thus, our findings open up the new perspective that resveratrol-induced intracellular pathways could be a target for prevention or treatment of obesity-associated endocrine and metabolic adverse effects. Am J Clin Nutr 2010; 92: 5-15.