NADPH酸化酵素による脂肪分化機構と生活習慣病への応用

肥胖症的特征在于由于新脂肪细胞的产生或个体脂肪细胞大小的增加而增加的脂肪组织质量。脂肪组织的形成涉及间充质干细胞（MSC）向前脂肪细胞谱系的定向分化以及前脂肪细胞分化为成熟脂肪细胞。为了研究调控MSC向脂肪细胞分化的分子机制，我们研究了活性氧（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）阻断脂肪细胞分化。H2 DCF分析显示，分化诱导剂诱导ROS产生。接下来，我们研究了ROS的来源。通过RNA干扰敲低NAD（P）H氧化酶4（Nox 4）抑制ROS的产生和分化诱导剂诱导的脂肪细胞分化。此外，我们研究了ROS在体内的作用。给予NAC减少了喂食高脂肪饮食的小鼠的脂肪量。这些结果将ROS鉴定为脂肪形成和肥胖的调节剂。

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.