CHARACTERIZATION OF THE METALLOME OF EXTREME PHYSICAL INACTIVITY IN HUMANS AND RODENTS

Mathieu HOREAU1, Olivier LORÉAL2, Frédéric DERBRÉ1, Nastassia NAVASIOLAVA 3,4, Angelique VAN OMBERGEN5, Marc-Antoine CUSTAUD3,4, Martine ROPERT2, Ines ANTUNES6, Marie-Pierre BAREILLE7, Guillemette GAUQUELIN-KOCH8, Rebecca BILLETTE DE VILLEMEUR7

1Movement, Sport and Health Laboratory , Rennes , France
2INSERM - UMR 1317, AEM2 platform, Nutrition Metabolisms and Cancer (NuMeCan) institute - University of Rennes, Rennes, France
3CRC, CHU Angers, Inserm, CNRS, MITOVASC, Equipe CARME, SFR ICAT - Université d'Angers , Angers , France
4Mitovasc UMR INSERM 1083-CNRS 6015, Universite d'Angers, Angers, France
5European Space Agency (ESA), Noordwijk, Netherlands
6Telespazio Belgium S.R.L. for the European Space Agency, Noordwijk, Netherlands
7Institute of Space Physiology and Medicine (MEDES), Toulouse, France
8Centre National d'Études Spatiales , Paris, France

This study aims to characterize, in humans and rodents, the response of the metallome to experimental models of extreme physical inactivity (EPI), specific to astronaut and bedridden patients, with a special focus on sex-related differences. Using Inductively Coupled Plasma/Mass Spectrometry, we analyzed six essential metals that constitute the plasma metallome of men and women exposed to 5 days of dry immersion (DI) and male and female rats subjected to 7 days of hindlimb unloading (HU). In rats, we also investigated the metallomic fingerprints of the liver, spleen, and skeletal muscles to identify potential metal redistributions.



At baseline, women had higher plasma Cu levels than men. In rats, females exhibited higher plasma levels of Fe and Cu, and lower concentrations of Mn. Under DI, plasma Fe and Zn levels increased in both sexes, and Cu levels increased only in men. In rats, HU resulted in elevated plasma Cu and Se levels in both sexes. Principal Component Analysis revealed organ and muscle type-specific metallomes in control groups. In the soleus, concentrations of Fe, Mg, Se, and Mn increased in HU females. In males, HU did not affect soleus Fe concentrations and promoted a decrease in Mg and Mn levels. In the gastrocnemius, irrespective of sex, HU led to increased Mg, Se, and Mn concentrations, with Cu, Zn, and Fe concentrations not significantly affected. In both sexes, the liver and spleen metallome was substantially affected by EPI.



Our data suggest that EPI profoundly affects plasma and organ metallome in both humans and rodents.