Department of Food Science, Purdue University, West Lafayette, IN 47907, USA.
Nutr Res. 2012 Aug;32(8):607-16. doi: 10.1016/j.nutres.2012.06.014. Epub 2012 Aug 3.
Resveratrol is known as a potent antiobesity compound that acts partly through inhibition of adipogenesis. However, the direct targets responsible for its antiadipogenic action are unclear. Our hypothesis is that resveratrol inhibits adipogenesis through modulation of mitotic clonal expansion (MCE) and cell signaling pathways in the early phase of differentiation. To test this, we examined the effects of resveratrol on MCE and insulin signaling pathway in the early phase of adipogenesis in murine preadipocytes. We observed that the antiadipogenic action of resveratrol is largely limited to the early phase of adipogenesis. Specifically, the presence of resveratrol in the first 24 hours of adipogenesis was required for its antiadipogenic effect. During the first 24 hours of adipogenesis, resveratrol impaired the progression of MCE by suppressing the cell cycle entry of preadipocytes to G2/M phase, and expression of cell cycle regulators cyclin A and cyclin-dependent kinase 2. Concomitantly, resveratrol inhibited insulin signaling pathway in the early phase of adipogenesis. Furthermore, we revealed an inhibitory effect of resveratrol on insulin receptor (IR) activity, and this is likely through a direct physical interaction between resveratrol and IR. The antiadipogenic effect of resveratrol is through inhibition of the MCE and IR-dependent insulin signaling pathway in the early phase of adipogenesis.
白藜芦醇是一种有效的抗肥胖化合物，其作用部分通过抑制脂肪生成。然而，负责其抗脂肪生成作用的直接靶标尚不清楚。我们的假设是，白藜芦醇通过调节有丝分裂克隆扩张（MCE）和细胞信号通路在分化的早期阶段来抑制脂肪生成。为了验证这一点，我们研究了白藜芦醇对小鼠前体脂肪细胞脂肪生成早期阶段的 MCE 和胰岛素信号通路的影响。我们观察到，白藜芦醇的抗脂肪生成作用主要限于脂肪生成的早期阶段。具体来说，白藜芦醇在脂肪生成的前 24 小时内存在是其抗脂肪生成作用所必需的。在脂肪生成的前 24 小时内，白藜芦醇通过抑制前体脂肪细胞进入 G2/M 期的细胞周期进入和细胞周期调节剂细胞周期蛋白 A 和细胞周期蛋白依赖性激酶 2 的表达来损害 MCE 的进展。同时，白藜芦醇在脂肪生成的早期阶段抑制胰岛素信号通路。此外，我们揭示了白藜芦醇对胰岛素受体（IR）活性的抑制作用，这可能是通过白藜芦醇和 IR 之间的直接物理相互作用。白藜芦醇的抗脂肪生成作用是通过抑制脂肪生成早期的 MCE 和 IR 依赖性胰岛素信号通路。
