Document Detail


Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice.
MedLine Citation:
PMID:  23281394     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.
Authors:
Paolo E Porporato; Nicoletta Filigheddu; Simone Reano; Michele Ferrara; Elia Angelino; Viola F Gnocchi; Flavia Prodam; Giulia Ronchi; Sharmila Fagoonee; Michele Fornaro; Federica Chianale; Gianluca Baldanzi; Nicola Surico; Fabiola Sinigaglia; Isabelle Perroteau; Roy G Smith; Yuxiang Sun; Stefano Geuna; Andrea Graziani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  611-22     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Acylation
Animals
Cachexia / metabolism,  prevention & control
Cell Line
Ghrelin / chemistry*,  metabolism,  pharmacology*
MAP Kinase Signaling System
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Multiprotein Complexes / metabolism
Muscle Denervation
Muscle, Skeletal / drug effects,  metabolism,  pathology
Muscular Atrophy / metabolism,  pathology,  prevention & control*
Protein Binding
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Ghrelin / metabolism
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
Grant Support
ID/Acronym/Agency:
GGP030386//Telethon
Chemical
Reg. No./Substance:
0/Ghrelin; 0/Multiprotein Complexes; 0/Receptors, Ghrelin; 0/TOR complex 2; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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