NADPH酸化酵素による脂肪分化機構と生活習慣病への応用

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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.