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Space travel induces stresses that contribute to health problems, as well as inducing the expression of Nrf2 (NF-E2-related factor-2) target genes that mediate adaptive responses to oxidative and other stress responses. The volume of epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change that is attenuated by  Nrf2  knockout. We conducted metabolome analyses of plasma from wild-type and  Nrf2  knockout mice collected at pre-flight, in-flight and post-flight time points, as well as tissues collected post-flight to clarify the metabolic responses during and after spaceflight and the contribution of Nrf2 to these responses. Plasma glycerophospholipid and sphingolipid levels were elevated during spaceflight, whereas triacylglycerol levels were lower after spaceflight. In wild-type mouse eWAT, triacylglycerol levels were increased, but phosphatidylcholine levels were decreased, and these changes were attenuated in  Nrf2  knockout mice. Transcriptome analyses revealed marked changes in the expression of lipid-related genes in the liver and eWAT after spaceflight and the effects of  Nrf2  knockout on these changes. Based on these results, we concluded that space stress provokes significant responses in lipid metabolism during and after spaceflight; Nrf2 plays critical roles in these responses.

Nrf2 plays a critical role in the metabolic response during and after spaceflight