Abstract

Skeletal muscle atrophy, a common consequence of disuse conditions like hindlimb unloading (HU), involves a complex interplay between anabolic and catabolic signaling pathways, often initiated by changes at the cellular membrane level. This study investigated the early protective effects of $\beta$-guanidinopropionic acid ($\beta$-GPA), a creatine analog, on the soleus muscle of rats subjected to the initial stage of HU. We hypothesized that $\beta$-GPA supplementation would modulate key signaling molecules to mitigate the catabolic shift. Methods involved administering $\beta$-GPA to rats before and during a short period of HU, followed by Western blot analysis of muscle tissue. Key markers of the Akt/mTOR anabolic pathway (e.g., phosphorylated Akt, p70S6K) and the ubiquitin-proteasome catabolic pathway (e.g., MuRF1, Atrogin-1) were quantified. Our findings indicate that $\beta$-GPA significantly attenuated the HU-induced decrease in anabolic signaling and partially suppressed the upregulation of catabolic markers. These results suggest that $\beta$-GPA acts rapidly to stabilize the cellular energy state and membrane-associated signaling cascades, offering a potential therapeutic strategy to counteract the initial molecular events leading to muscle disuse atrophy. Further research is warranted to elucidate the precise membrane-receptor or transporter mechanisms through which $\beta$-GPA exerts its protective effects.