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However, the mechanism underlying prolonged muscle disuse\u2010induced mTORC1 signaling activation remains unclear. The mevalonate pathway activates the mTORC1 signaling pathway via the prenylation and activation of Ras homolog enriched in brain (Rheb). Therefore, we investigated the effects of hindlimb unloading (HU) for 14\u2009days on the mevalonate and mTORC1 signaling pathways in the plantaris muscle, a fast\u2010twitch muscle, in adult male rats. Rats were divided into HU and control groups. The plantaris muscles of both groups were harvested after the treatment period, and the expression and phosphorylation levels of metabolic and intracellular signaling proteins were analyzed using Western blotting. We found that HU increased the expression of 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A reductase, the rate\u2010limiting enzyme of the mevalonate pathway, and activated the mTORC1 signaling pathway without activating AKT, an upstream activator of mTORC1. Furthermore, HU increased prenylated Rheb. Collectively, these findings suggest that the activated mevalonate pathway may be involved in the activation of the Rheb\/mTORC1 signaling pathway without AKT activation in fast\u2010twitch muscles under prolonged disuse conditions.<\/jats:p>","DOI":"10.14814\/phy2.15969","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T01:54:54Z","timestamp":1709862894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of hindlimb unloading on the mevalonate and mechanistic target of rapamycin complex 1 signaling pathways in a fast\u2010twitch muscle in rats"],"prefix":"10.14814","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-7035","authenticated-orcid":false,"given":"Munehiro","family":"Uda","sequence":"first","affiliation":[{"name":"School of Nursing Hirosaki Gakuin University  Hirosaki Aomori 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