Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus C, Denmark.
Int J Obes (Lond). 2010 Oct;34(10):1546-53. doi: 10.1038/ijo.2010.98. Epub 2010 Jun 8.
Human obesity is closely associated with a state of chronic low-grade inflammation, which also involves the adipose tissue with enhanced production of bioactive substances (adipokines). Calorie restriction (CR) reduces adipocytokine production and improves metabolic profile in rodents. Some of these effects are mediated through activation of the sirtuin 1 (Sirt1) enzyme, and in this study, we investigate whether the natural phytoalexin, resveratrol (RSV), which is a potent Sirt1 activator, has anti-inflammatory effects in human adipose tissue explants.
The effect of RSV on interleukin 1β (IL1β)-induced change of adipokine mRNA gene expression and secretion were measured in human adipose tissue explants.
Exposure of human adipose tissue in vitro to IL1β for 24 h increased secretion of the proinflammatory adipokines IL6, IL8 and monocyte chemoattractant protein 1 (MCP-1) 3-7.7-fold (P<0.05) and increased IL6, IL8, MCP-1, IL1β and PAI-1 mRNA expression 1.3-7.2-fold (P<0.05) accordingly. Concomitant incubations with RSV reversed the IL1β-stimulated secretion (16-36%) and gene expression (25-48%) of these adipokines. IL1β reduced adiponectin mRNA expression (40%), a decrement that was reversed by RSV treatment. Similar effects were observed in differentiated human preadipocytes in primary culture, indicating that human adipocytes are a potential target for RSV effects. Finally, the effects were neutralized by sirtinol, a Sirt1 inhibitor.
This study is the first to show anti-inflammatory effects of RSV on adipokine expression and secretion in human adipose tissue in vitro through the SIRT1 pathway. Thus, RSV is hypothesized to possess beneficial effects and might improve the metabolic profile in human obesity.
人体肥胖与慢性低度炎症状态密切相关,这种炎症状态还涉及到脂肪组织,导致生物活性物质(脂肪因子)的产生增加。热量限制(CR)可减少脂肪细胞因子的产生,并改善啮齿动物的代谢状况。其中一些作用是通过激活沉默调节蛋白 1(Sirt1)酶来介导的,在这项研究中,我们研究了天然植物抗毒素白藜芦醇(RSV)是否对人体脂肪组织外植体具有抗炎作用,因为 RSV 是一种有效的 Sirt1 激活剂。
在人体脂肪组织外植体中测量 RSV 对白细胞介素 1β(IL1β)诱导的脂肪因子 mRNA 基因表达和分泌变化的影响。
在体外将人类脂肪组织暴露于 IL1β 24 小时可使促炎脂肪因子 IL6、IL8 和单核细胞趋化蛋白 1(MCP-1)的分泌增加 3-7.7 倍(P<0.05),并相应地使 IL6、IL8、MCP-1、IL1β 和 PAI-1mRNA 表达增加 1.3-7.2 倍(P<0.05)。同时孵育 RSV 可逆转 IL1β 刺激的这些脂肪因子的分泌(16-36%)和基因表达(25-48%)。IL1β 降低了脂联素 mRNA 表达(40%),而 RSV 处理可逆转这一降低。在原代培养的分化人前脂肪细胞中也观察到类似的效果,表明人脂肪细胞可能是 RSV 作用的潜在靶标。最后,这些作用被 Sirt1 抑制剂 sirtinol 中和。
这项研究首次表明,RSV 通过 SIRT1 途径在体外对人脂肪组织中脂肪因子的表达和分泌具有抗炎作用。因此,RSV 被假设具有有益的作用,并可能改善人体肥胖的代谢状况。