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

Abdominal Fat / pathology Adipose Tissue, White / pathology Aging / blood Animals Bone and Bones / pathology Gene Expression Regulation Homeostasis Metabolome Mice, Knockout Muscles / pathology NF-E2-Related Factor 2 / deficiency Sequence Analysis, RNA Space Flight Stress, Physiological Weight Gain / genetics

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
08 09 2020
Historique:
received: 15 04 2020
accepted: 13 08 2020
entrez: 9 9 2020
pubmed: 10 9 2020
medline: 17 6 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s42003-020-01227-2 PMID: 32901092 PMC: PMC7479603
pubmed: 32901092
doi: 10.1038/s42003-020-01227-2
pii: 10.1038/s42003-020-01227-2
pmc: PMC7479603
doi:

Substances chimiques

NF-E2-Related Factor 2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

496

Subventions

Organisme : NCI NIH HHS
ID : R35 CA197222
Pays : United States

Commentaires et corrections

Type : ErratumIn

Références

Demontis, G. C. et al. Human pathophysiological adaptations to the space environment. Front. Physiol. 8, 547 (2017).
pubmed: 5539130 pmcid: 5539130 doi: 10.3389/fphys.2017.00547
Pecaut, M. J. et al. Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions. J. Appl. Physiol. 94, 2085–2094 (2003).
doi: 10.1152/japplphysiol.01052.2002 pubmed: 12514166
Baqai, F. P. et al. Effects of spaceflight on innate immune function and antioxidant gene expression. J. Appl. Physiol. 106, 1935–1942 (2009).
pubmed: 2692779 pmcid: 2692779 doi: 10.1152/japplphysiol.91361.2008
Behnke, B. J. et al. Effects of spaceflight and ground recovery on mesenteric artery and vein constrictor properties in mice. FASEB J. 27, 399–409 (2013).
pubmed: 4050424 pmcid: 4050424 doi: 10.1096/fj.12-218503
Gridley, D. S. et al. Changes in mouse thymus and spleen after return from the STS-135 mission in space. PLoS ONE 8, e75097 (2013).
pubmed: 3777930 pmcid: 3777930 doi: 10.1371/journal.pone.0075097
Andreev-Andrievskiy, A. et al. Mice in Bion-M 1 space mission: training and selection. PLoS ONE 9, e104830 (2014).
pubmed: 4136787 pmcid: 4136787 doi: 10.1371/journal.pone.0104830
Ulanova, A. et al. Isoform composition and gene expression of thick and thin filament proteins in striated muscles of mice after 30-day space flight. Biomed. Res. Int. 2015, 104735 (2015).
pubmed: 4312622 pmcid: 4312622 doi: 10.1155/2015/104735
Cancedda, R. et al. The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice. PLoS ONE 7, e32243 (2012).
pubmed: 3362598 pmcid: 3362598 doi: 10.1371/journal.pone.0032243
Tavella, S. et al. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS). PLoS ONE 7, e33179 (2012).
pubmed: 3305296 pmcid: 3305296 doi: 10.1371/journal.pone.0033179
Sandonà, D. et al. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. PLoS ONE 7, e33232 (2012).
pubmed: 3314659 pmcid: 3314659 doi: 10.1371/journal.pone.0033232
Shiba, D. et al. Development of new experimental platform ‘MARS’-Multiple Artificial-gravity Research System-to elucidate the impacts of micro/partial gravity on mice. Sci. Rep. 7, 10837 (2017).
pubmed: 5589811 pmcid: 5589811 doi: 10.1038/s41598-017-10998-4
Matsuda, C. et al. Dietary intervention of mice using an improved Multiple Artificial-gravity Research System (MARS) under artificial 1. NPJ Microgravity 5, 16 (2019).
pubmed: 6614370 pmcid: 6614370 doi: 10.1038/s41526-019-0077-0
Yamamoto, M., Kensler, T. W. & Motohashi, H. The KEAP1-NRF2 System: a thiol-based sensor-effector apparatus for maintaining redox homeostasis. Physiol. Rev. 98, 1169–1203 (2018).
doi: 10.1152/physrev.00023.2017 pubmed: 29717933
Hosoya, T. et al. Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J. Biol. Chem. 280, 27244–27250 (2005).
doi: 10.1074/jbc.M502551200 pubmed: 15917255
Indo, H. P. et al. Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space. Sci. Rep. 6, 39015 (2016).
pubmed: 5159838 pmcid: 5159838 doi: 10.1038/srep39015
Itoh, K. et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys. Res. Commun. 236, 313–322 (1997).
doi: 10.1006/bbrc.1997.6943 pubmed: 9240432
Koshiba, S. et al. The structural origin of metabolic quantitative diversity. Sci. Rep. 6, 31463 (2016).
pubmed: 4985752 pmcid: 4985752 doi: 10.1038/srep31463
Koshiba, S. et al. Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project. Genes Cells 23, 406–417 (2018).
doi: 10.1111/gtc.12588 pubmed: 29701317
Saigusa, D. et al. Establishment of protocols for global metabolomics by LC-MS for biomarker discovery. PLoS ONE 11, e0160555 (2016).
pubmed: 5006994 pmcid: 5006994 doi: 10.1371/journal.pone.0160555
Kim, J. W. et al. Characterizing genomic alterations in cancer by complementary functional associations. Nat. Biotechnol. 34, 539–546 (2016).
pubmed: 4868596 pmcid: 4868596 doi: 10.1038/nbt.3527
Tominari, T. et al. Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice. Sci. Rep. 9, 6614 (2019).
pubmed: 6488638 pmcid: 6488638 doi: 10.1038/s41598-019-42829-z
Tadaka, S. et al. jMorp: Japanese multi omics reference panel. Nucleic Acids Res. 46, D551–D557 (2018).
doi: 10.1093/nar/gkx978 pubmed: 29069501
Huber, J. D. Diabetes, cognitive function, and the blood-brain barrier. Curr. Pharm. Des. 14, 1594–1600 (2008).
doi: 10.2174/138161208784705441 pubmed: 18673200
Tahergorabi, Z. & Khazaei, M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler. 9, 247–253 (2013).
pubmed: 3746949 pmcid: 3746949
Lehrke, M. & Lazar, M. A. The many faces of PPARγ. Cell 123, 993–999 (2005).
doi: 10.1016/j.cell.2005.11.026 pubmed: 16360030
Suzuki, T. et al. Molecular mechanism of cellular oxidative stress sensing by Keap1. Cell Rep. 28, 746–758.e744 (2019).
doi: 10.1016/j.celrep.2019.06.047 pubmed: 31315052
Lönnqvist, F., Nyberg, B., Wahrenberg, H. & Arner, P. Catecholamine-induced lipolysis in adipose tissue of the elderly. J. Clin. Investig. 85, 1614–1621 (1990).
doi: 10.1172/JCI114612 pubmed: 2159025
Weil-Malherbe, H., Smith, E. R. & Bowles, G. R. Excretion of catecholamines and catecholamine metabolites in Project Mercury pilots. J. Appl. Physiol. 24, 146–151 (1968).
doi: 10.1152/jappl.1968.24.2.146 pubmed: 5637676
Miller, R. A. et al. Glycine supplementation extends lifespan of male and female mice. Aging Cell 18, e12953 (2019).
pubmed: 6516426 pmcid: 6516426 doi: 10.1111/acel.12953
Hashizume, O. et al. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects. Sci. Rep. 5, 10434 (2015).
pubmed: 5377050 pmcid: 5377050 doi: 10.1038/srep10434
Suzuki, T. et al. Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels. Mol. Cell Biol. 33, 2402–2412 (2013).
pubmed: 3700104 pmcid: 3700104 doi: 10.1128/MCB.00065-13
Cho, H. Y. et al. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am. J. Respir. Cell Mol. Biol. 26, 42–51 (2002).
doi: 10.1165/ajrcmb.26.1.4536 pubmed: 11751202
Cuadrado, A. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 18, 295–317 (2019).
doi: 10.1038/s41573-018-0008-x pubmed: 30610225
Yagishita, Y., Fahey, J. W., Dinkova-Kostova, A. T. & Kensler, T. W. Broccoli or sulforaphane: is it the source or dose that matters? Molecules https://doi.org/10.3390/molecules24193593 (2019).
Skoko, J. J. et al. Loss of Nrf2 in mice evokes a congenital intrahepatic shunt that alters hepatic oxygen and protein expression gradients and toxicity. Toxicol. Sci. 141, 112–119 (2014).
pubmed: 4271119 pmcid: 4271119 doi: 10.1093/toxsci/kfu109
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
doi: 10.1093/bioinformatics/bts635 pubmed: 23104886
Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform. 12, 323 (2011).
doi: 10.1186/1471-2105-12-323
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 25516281 doi: 10.1186/s13059-014-0550-8
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
doi: 10.1073/pnas.0506580102
Kuleshov, M. V. et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90–W97 (2016).
pubmed: 4987924 pmcid: 4987924 doi: 10.1093/nar/gkw377
Parlee, S. D., Lentz, S. I., Mori, H. & MacDougald, O. A. Quantifying size and number of adipocytes in adipose tissue. Methods Enzymol. 537, 93–122 (2014).
pubmed: 4069255 pmcid: 4069255 doi: 10.1016/B978-0-12-411619-1.00006-9
Wang, J. et al. Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet. Biochem. Biophys. Res. Commun. 489, 432–438 (2017).
Thompson, J. W. et al. International Ring Trial of a high resolution targeted metabolomics and lipidomics platform for serum and plasma analysis. Anal. Chem. 91, 14407–14416 (2019).
doi: 10.1021/acs.analchem.9b02908 pubmed: 31638379 pmcid: 7310668
Edgar, R., Domrachev, M. & Lash, A. E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210 (2002).
pubmed: 99122 pmcid: 99122 doi: 10.1093/nar/30.1.207

Auteurs

Takafumi Suzuki (T)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
ORCID: 0000-0002-3425-8208

Akira Uruno (A)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

Akane Yumoto (A)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan.

Keiko Taguchi (K)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, Sendai, Japan.

Mikiko Suzuki (M)

Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Japan.
ORCID: 0000-0003-3237-9919

Nobuhiko Harada (N)

Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai, Japan.

Rie Ryoke (R)

Department of Functional Brain Imaging, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.

Eriko Naganuma (E)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Nanae Osanai (N)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Aya Goto (A)

Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Hiromi Suda (H)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Ryan Browne (R)

Department of Functional Brain Imaging, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.

Akihito Otsuki (A)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
ORCID: 0000-0003-1516-1010

Fumiki Katsuoka (F)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, Sendai, Japan.

Michael Zorzi (M)

Department of Molecular Biotechnology and Health Sciences, University of Turin, 10125, Torino, Italy.
ORCID: 0000-0003-1245-3587

Takahiro Yamazaki (T)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

Daisuke Saigusa (D)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

Seizo Koshiba (S)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, Sendai, Japan.

Takashi Nakamura (T)

Division of Molecular Pharmacology & Cell Biophysics, Tohoku University Graduate School of Dentistry, Sendai, Japan.
ORCID: 0000-0001-9904-1037

Satoshi Fukumoto (S)

Division of Pediatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.

Hironobu Ikehata (H)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Keizo Nishikawa (K)

Immunology Frontier Research Center, Osaka University, Suita, Japan.

Norio Suzuki (N)

Division of Oxygen Biology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Ikuo Hirano (I)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Ritsuko Shimizu (R)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Tetsuya Oishi (T)

Division of Oxygen Biology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Hozumi Motohashi (H)

Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
ORCID: 0000-0002-7261-1033

Hirona Tsubouchi (H)

Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Risa Okada (R)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan.
Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Takashi Kudo (T)

Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Michihiko Shimomura (M)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan.

Thomas W Kensler (TW)

Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
ORCID: 0000-0002-6676-261X

Hiroyasu Mizuno (H)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan.

Masaki Shirakawa (M)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan.

Satoru Takahashi (S)

Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
ORCID: 0000-0002-8540-7760

Dai Shiba (D)

JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Japan. shiba.dai@jaxa.jp.

Masayuki Yamamoto (M)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. masiyamamoto@med.tohoku.ac.jp.
Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. masiyamamoto@med.tohoku.ac.jp.
The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, Sendai, Japan. masiyamamoto@med.tohoku.ac.jp.
ORCID: 0000-0002-9073-9436

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › Graisse abdominale › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux blanc › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Eucaryotes › Animaux › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Tissus › Tissu conjonctif › Os et tissu osseux › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Métabolisme › Métabolome › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Tissus › Muscles › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteur-2 apparenté à NF-E2 › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Technologie, industrie et agriculture › Transports › Aviation › Vol spatial › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Phénomènes physiologiques › Stress physiologique › Nrf2 contributes to the weight gain of mice...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Mensurations corporelles › Poids › Modifications du poids corporel › Prise de poids › Nrf2 contributes to the weight gain of mice...