title: Fatigue-induced Orosomucoid 1 Acts on C-C Chemokine Receptor Type 5 to Enhance Muscle Endurance.
abstract: Understanding and managing fatigue is a significant challenge in clinic and society. In attempting to explore how the body responds to and regulates fatigue, we found in rodent fatigue models that orosomucoid 1 (ORM1) was significantly increased in multiple tissues, including blood and muscle. Interestingly, administration of exogenous ORM1 increased muscle glycogen and enhanced muscle endurance, whereas ORM1 deficiency resulted in a significant decrease of muscle endurance both in vivo and in vitro, which could largely be restored by exogenous ORM1. Further studies demonstrated that ORM1 can bind to C-C chemokine receptor type 5 (CCR5) on muscle cells and deletion of the receptor abolished the effect of ORM1. Thus, fatigue upregulates the level of ORM1, which in turn functions as an anti-fatigue protein to enhance muscle endurance via the CCR5 pathway. Modulation of the level of ORM1 and CCR5 signaling could be a novel strategy for the management of fatigue.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zhumin
authors.initials: Z
authors.lastname: Luo
authors.affiliation: DL Biotech USA, Gaithersburg, MD, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Yourek
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Gui
authors.affiliation: Laboratory of Translational Medicine, Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou 215123, Jiangsu, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008810:Mice, Inbred C57BL; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000502:physiology; D009961:Orosomucoid / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D019713:Receptors, CCR5 / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D009961:Orosomucoid; D019713:Receptors, CCR5