NADPH酸化酵素による脂肪分化機構と生活習慣病への応用

肥胖的特征是由于新脂肪细胞的生成或单个脂肪细胞大小的增加而导致脂肪组织质量增加。脂肪组织的形成涉及到间充质干细胞(MSC)对前脂肪细胞谱系的承诺和前脂肪细胞向成熟脂肪细胞的分化。为了探讨MSC向脂肪细胞分化的分子机制，我们研究了ROS在脂肪细胞分化中的作用。我们发现抗氧化剂N-乙酰-L-半胱氨酸(NAC)可阻断脂肪细胞的分化。H_2DCF分析表明，分化诱导剂诱导ROS的产生。接下来，我们考察了ROS的来源。RNA干扰抑制NAD(P)H氧化酶4(NOX4)的表达，抑制ROS的产生，抑制分化诱导剂诱导的脂肪细胞分化。此外，我们还研究了ROS在体内的作用。服用NAC可减少高脂饮食小鼠的脂肪量。这些结果表明，ROS是脂肪生成和肥胖的调节因子。

Obesity is characterized by increased adipose tissue mass due to generation of new adipocytes or increase in the size of individual adipocytes. The formation of adipose tissue involves the commitment of mesenchymal stem cells (MSC) to the preadipocyte lineage and the differentiation of preadipocytes into mature adipocytes. To investigate the molecular mechanisms that regulate the differentiation of adipocytes from MSC, we investigated the involvement of reactive oxygen species (ROS) in adipocyte differentiation. We found that the antioxidant N-acetyl-L-cysteine (NAC) blocks adipocyte differentiation. An H2DCF assay revealed that differentiation-inducing agents induced ROS generation. Next, we examined the source of ROS. Knockdown of NAD(P)H oxidase 4 (Nox4) by RNA interference inhibited ROS production and adipocyte differentiation by differentiation-inducing agents. Furthermore, we examined the role of ROS in vivo. Administrating the NAC reduced the amount of fat in mice fed a high fat diet. These results identify ROS as a regulator of the adipogenesis and obesity.