TY - JOUR
T1 - Nrf2 plays a critical role in the metabolic response during and after spaceflight
AU - Uruno, Akira
AU - Saigusa, Daisuke
AU - Suzuki, Takafumi
AU - Yumoto, Akane
AU - Nakamura, Tomohiro
AU - Matsukawa, Naomi
AU - Yamazaki, Takahiro
AU - Saito, Ristumi
AU - Taguchi, Keiko
AU - Suzuki, Mikiko
AU - Suzuki, Norio
AU - Otsuki, Akihito
AU - Katsuoka, Fumiki
AU - Hishinuma, Eiji
AU - Okada, Risa
AU - Koshiba, Seizo
AU - Tomioka, Yoshihisa
AU - Shimizu, Ritsuko
AU - Shirakawa, Masaki
AU - Kensler, Thomas W.
AU - Shiba, Dai
AU - Yamamoto, Masayuki
N1 - Funding Information:
We would like to thank Norishige Kanai (astronaut) for performing the onboard operations and Toshiaki Kokubo and Noriko Kajiwara (JAXA visiting veterinarians) for monitoring mouse health. We also thank Naoko Ota-Murakami, Fumika Yamaguchi, Masumi Umehara, and the members of the mouse health check team for performing daily onboard health checks; Ramona Bober, Autumn L. Cdebaca and Rebecca A. Smith for providing animal care and support of ground experiments; Hirochika Murase, Hir-oaki Kodama, Yusuke Hagiwara and members of the hardware development team for MHU hardware preparation and operations; Kohei Hirakawa, Teruhiro Senkoji, Haruna Tanii, Motoki Tada, Yuki Watanabe, Kayoko Iino, Hiromi Sano, Yui Nakata, Hiromi Suzuki-Hashizume, Eiji Ohta, Osamu Funatsu, Hideaki Hotta, Hatsumi Ishida, Mariko Shimizu and members of the JEM operational team for research coordination; Takahashi Ueda and Tomohiro Tamari for animal preparation; Hong Xin and Grishma Acharya for landing site operational support; and Sayaka Umemura, Laura Lewis, Charles E. Hopper, Jennifer J. Scott Williams, and Robert Kuczajda for international coordination. This work was selected as a space rodent research study for JAXA feasibility experiments using ISS/ Kibo announced in 2015 and supported in part by the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from the Japan Agency for Medical Research and Development (AMED) [grant number JP19am0101001 (M.Y.)], the Tohoku Medical Megabank Project from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the AMED [JP20km0105001 and JP20km0105002 (M.Y.)], Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) [grant numbers 19H05649 (M.Y.) and 20K07352 (A.U.)], and the Smart Aging Research Center at Tohoku University.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-021-02904-6
DO - 10.1038/s42003-021-02904-6
M3 - Article
AN - SCOPUS:85121004717
VL - 4
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 1381
ER -