Mouse hindlimb unloading, as a model of simulated microgravity, leads to dysregulated iron homeostasis in liver and skeletal muscle cells

Abstract

Microgravity exposure can impact various physiological systems, yet its specific effects on liver cells remain inadequately studied. To address this gap, we used a hindlimb unloading (HU) mouse model to simulate microgravity conditions and investigate alterations in iron metabolism within liver and skeletal muscle cells. 16-week-old male C57BL/6j mice were divided into three groups: (i) ground-based control (GC), (ii) hindlimb unloading treated with vehicle (HU-v), and (iii) hindlimb unloading treated with deferoxamine (DFO). After three weeks, mice were euthanized, and samples of gastrocnemius muscle, liver, and serum were collected for analysis. The HU-v group exhibited significant muscle and liver cell atrophy compared to the GC group, along with disrupted iron metabolism, as indicated by altered expression of key iron regulatory proteins, including FTH1, FPN, TFR1, IRP-1, HMOX-1, and Hepcidin. In contrast, the DFO group demonstrated restored iron homeostasis, with protein expression patterns resembling those of the GC group. Serum analysis revealed elevated levels of serum iron, ferritin, and transferrin in the DFO group compared to both HU-v and GC groups, albeit with minimal changes in total iron-binding capacity. These findings suggest that simulated microgravity induces iron overload and cellular atrophy in liver and skeletal muscle cells, highlighting the potential therapeutic benefits of iron chelation in such conditions.

Keywords: Hindlimb unloading; Iron homeostasis; Liver; Microgravity; Skeletal muscles.