Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

Geraldine Vitry; Rebecca Finch; Gavin Mcstay; Afshin Behesti; Sébastien Déjean; Tricia Larose; Virginia Wotring; Willian Abraham da Silveira

doi:10.1016/j.isci.2022.105213

Muscle atrophy phenotype gene expression during spaceflight is linked to a metabolic crosstalk in both the liver and the muscle in mice

iScience. 2022 Sep 24;25(10):105213. doi: 10.1016/j.isci.2022.105213. eCollection 2022 Oct 21.

Authors

Geraldine Vitry^{1

2}, Rebecca Finch², Gavin Mcstay², Afshin Behesti^{3

4}, Sébastien Déjean⁵, Tricia Larose^{1

6}, Virginia Wotring^{1

7}, Willian Abraham da Silveira^{1

2}

Affiliations

¹ International Space University, 67400 Illkirch-Graffenstaden, France.
² Staffordshire University, Department of Biological Sciences, School of Health, Science and Wellbeing, Staffordshire University, Science Centre, Leek Road, Stoke-on-Trent ST4 2DF, UK.
³ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁵ Institut de Mathématiques de Toulouse, UMR5219, Université de Toulouse, CNRS, UPS, Cedex 9, 31062 Toulouse, France.
⁶ Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway.
⁷ Center for Space Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Human expansion in space is hampered by the physiological risks of spaceflight. The muscle and the liver are among the most affected tissues during spaceflight and their relationships in response to space exposure have never been studied. We compared the transcriptome response of liver and quadriceps from mice on NASA RR1 mission, after 37 days of exposure to spaceflight using GSEA, ORA, and sparse partial least square-differential analysis. We found that lipid metabolism is the most affected biological process between the two organs. A specific gene cluster expression pattern in the liver strongly correlated with glucose sparing and an energy-saving response affecting high energy demand process gene expression such as DNA repair, autophagy, and translation in the muscle. Our results show that impaired lipid metabolism gene expression in the liver and muscle atrophy gene expression are two paired events during spaceflight, for which dietary changes represent a possible countermeasure.

Keywords: Astronautics; Omics; Space medicine; Space sciences.