title: Therapeutic potential of ghrelin treatment for unloading-induced muscle atrophy in mice.
abstract: Ghrelin is a growth hormone (GH) secretagogue secreted mainly from the stomach that functions in controlling muscle volume and energy homeostasis. We here studied the effects of ghrelin on unloading-induced muscle atrophy using a mouse model of hindlimb suspension (HS). Ghrelin administration during 2-week HS alleviated reductions of muscle mass in the fast-twitch fiber-rich plantaris muscle and the slow-twitch fiber-rich soleus muscle of the hindlimb. Ghrelin administration during a 5-day recovery period following 2-week HS enhanced food intake and facilitated recovery from atrophy in both muscles. Ghrelin administration normalized hypercorticosteronemia in these studies. Ghrelin's anti-muscle atrophy effect was found even under pair-feeding condition, but not in mice given des-acyl ghrelin. Insulin-like growth factor (IGF)-1 mRNA expression was significantly reduced in the atrophied plantaris muscle compared with control muscles. A single ghrelin administration to HS mice acutely increased plasma GH and also amplified phosphorylation of signal transducer and activator of transcription (STAT) 5 and increased IGF-1 mRNA expression in the plantaris muscle, but not in the soleus muscle. This study demonstrated that ghrelin stimulated the GH-STAT5-IGF-1 axis in the locally atrophied plantaris muscle, and its administration alleviated muscle atrophy and facilitated recovery from muscle atrophy. Ghrelin's effects represent a novel therapeutic paradigm for the treatment of unloading-induced muscle atrophy induced by factors such as bed rest, injury, and joint immobilization.
authors.affiliation: Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koshinaka
authors.forename: Koji
authors.initials: K
authors.lastname: Toshinai
authors.forename: Arif
authors.initials: A
authors.lastname: Mohammad
authors.forename: Kenji
authors.initials: K
authors.lastname: Noma
authors.forename: Miki
authors.initials: M
authors.lastname: Oshikawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ueno
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
mesh_terms: D000818:Animals; D054439:Ghrelin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019417:Hindlimb Suspension; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D050799:STAT5 Transcription Factor / Q000378:metabolism
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D007334:Insulin-Like Growth Factor I