Intermittent reloading does not prevent reduction in iron availability and hepcidin upregulation caused by hindlimb unloading

Journal article


Nay, Kévin, Martin, David, Orfila, Luz, Saligaut, Dany, Martin, Brice, Horeau, Mathieu, Cavey, Thibaut, Kenawi, Moussa, Island, Marie-Laure, Ropert, Martine, Loréal, Olivier, Koechlin-Ramonatxo, Christelle and Derbré, Frédéric. (2021). Intermittent reloading does not prevent reduction in iron availability and hepcidin upregulation caused by hindlimb unloading. Experimental Physiology. 106(1), pp. 28-36. https://doi.org/10.1113/EP088339
AuthorsNay, Kévin, Martin, David, Orfila, Luz, Saligaut, Dany, Martin, Brice, Horeau, Mathieu, Cavey, Thibaut, Kenawi, Moussa, Island, Marie-Laure, Ropert, Martine, Loréal, Olivier, Koechlin-Ramonatxo, Christelle and Derbré, Frédéric
Abstract

In humans, exposure to microgravity during spaceflight causes muscle atrophy, changes in iron storage and a reduction in iron availability. We previously observed that during 7 days of simulated microgravity in rats, hepcidin plays a key role in iron misdistribution, and we suggested that a crosstalk between skeletal muscle and liver could regulate hepcidin synthesis in this context. In the present study in rats, we investigated the medium-term effects of simulated microgravity on iron metabolism. We also tested whether intermittent reloading (IR) to target skeletal muscle atrophy limits iron misdistribution efficiently. For this purpose, Wistar rats underwent 14 days of hindlimb unloading (HU) combined or not combined with daily IR. At the end of this period, the serum iron concentration and transferrin saturation were significantly reduced, whereas hepatic hepcidin mRNA was upregulated. However, the main signalling pathways involved in hepcidin synthesis in the liver (BMP–small mothers against decapentaplegic (SMAD), interleukin-6–STAT3 and ERK1/2) were unaffected. Unlike what was observed after 7 days of HU, the iron concentration in the spleen, liver and skeletal muscle was comparable between control animals and those that underwent HU or HU plus IR for 14 days. Despite its beneficial effect on soleus muscle atrophy and slow-to-fast myosin heavy chain distribution, IR did not significantly prevent a reduction in iron availability and hepcidin upregulation. Altogether, these results highlight that iron availability is durably reduced during longer exposure to simulated microgravity and that the related hepcidin upregulation is not a transient adaptation to these conditions. The results also suggest that skeletal muscle does not necessarily play a key role in the iron misdistribution that occurs during simulated microgravity.

Keywordscrosstalk; disuse; iron overload; myosin heavy chain; physical inactivity
Year2021
JournalExperimental Physiology
Journal citation106 (1), pp. 28-36
PublisherBlackwell Publishing Ltd
ISSN0958-0670
Digital Object Identifier (DOI)https://doi.org/10.1113/EP088339
Scopus EID2-s2.0-85085512240
Research or scholarlyResearch
Page range28-36
Publisher's version
License
All rights reserved
File Access Level
Controlled
Output statusPublished
Publication dates
Online13 Apr 2020
Publication process dates
Accepted09 Apr 2020
Deposited28 Jun 2021
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