Nrf2 contributes to the weight gain of mice during space travel.

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans. Using Nrf2 knockout mice, Suzuki, Uruno, Yumoto et al. show that space travel activates Nrf2 signaling, which contributes to the weight gain of mice by regulating fat metabolism of white adipose tissues. This study provides insights into potential interventions to mitigate stresses that accompany space travels.