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Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation
Despite being unable to activate the cognate ghrelin receptor (GHS-R), unacylated ghrelin (UAG) possesses a unique activity spectrum that includes promoting bone marrow adipogenesis. Since a receptor mediating this action has not been identified, we re-appraised the potential interaction of UAG with...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374529/ https://www.ncbi.nlm.nih.gov/pubmed/28361877 http://dx.doi.org/10.1038/srep45541 |
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author | Hopkins, Anna L. Nelson, Timothy A. S. Guschina, Irina A. Parsons, Lydia C. Lewis, Charlotte L. Brown, Richard C. Christian, Helen C. Davies, Jeffrey S. Wells, Timothy |
author_facet | Hopkins, Anna L. Nelson, Timothy A. S. Guschina, Irina A. Parsons, Lydia C. Lewis, Charlotte L. Brown, Richard C. Christian, Helen C. Davies, Jeffrey S. Wells, Timothy |
author_sort | Hopkins, Anna L. |
collection | PubMed |
description | Despite being unable to activate the cognate ghrelin receptor (GHS-R), unacylated ghrelin (UAG) possesses a unique activity spectrum that includes promoting bone marrow adipogenesis. Since a receptor mediating this action has not been identified, we re-appraised the potential interaction of UAG with GHS-R in the regulation of bone marrow adiposity. Surprisingly, the adipogenic effects of intra-bone marrow (ibm)-infused acylated ghrelin (AG) and UAG were abolished in male GHS-R-null mice. Gas chromatography showed that isolated tibial marrow adipocytes contain the medium-chain fatty acids utilised in the acylation of UAG, including octanoic acid. Additionally, immunohistochemistry and immunogold electron microscopy revealed that tibial marrow adipocytes show prominent expression of the UAG-activating enzyme ghrelin O-acyl transferase (GOAT), which is located in the membranes of lipid trafficking vesicles and in the plasma membrane. Finally, the adipogenic effect of ibm-infused UAG was completely abolished in GOAT-KO mice. Thus, the adipogenic action of exogenous UAG in tibial marrow is dependent upon acylation by GOAT and activation of GHS-R. This suggests that UAG is subject to target cell-mediated activation – a novel mechanism for manipulating hormone activity. |
format | Online Article Text |
id | pubmed-5374529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53745292017-04-03 Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation Hopkins, Anna L. Nelson, Timothy A. S. Guschina, Irina A. Parsons, Lydia C. Lewis, Charlotte L. Brown, Richard C. Christian, Helen C. Davies, Jeffrey S. Wells, Timothy Sci Rep Article Despite being unable to activate the cognate ghrelin receptor (GHS-R), unacylated ghrelin (UAG) possesses a unique activity spectrum that includes promoting bone marrow adipogenesis. Since a receptor mediating this action has not been identified, we re-appraised the potential interaction of UAG with GHS-R in the regulation of bone marrow adiposity. Surprisingly, the adipogenic effects of intra-bone marrow (ibm)-infused acylated ghrelin (AG) and UAG were abolished in male GHS-R-null mice. Gas chromatography showed that isolated tibial marrow adipocytes contain the medium-chain fatty acids utilised in the acylation of UAG, including octanoic acid. Additionally, immunohistochemistry and immunogold electron microscopy revealed that tibial marrow adipocytes show prominent expression of the UAG-activating enzyme ghrelin O-acyl transferase (GOAT), which is located in the membranes of lipid trafficking vesicles and in the plasma membrane. Finally, the adipogenic effect of ibm-infused UAG was completely abolished in GOAT-KO mice. Thus, the adipogenic action of exogenous UAG in tibial marrow is dependent upon acylation by GOAT and activation of GHS-R. This suggests that UAG is subject to target cell-mediated activation – a novel mechanism for manipulating hormone activity. Nature Publishing Group 2017-03-31 /pmc/articles/PMC5374529/ /pubmed/28361877 http://dx.doi.org/10.1038/srep45541 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Hopkins, Anna L. Nelson, Timothy A. S. Guschina, Irina A. Parsons, Lydia C. Lewis, Charlotte L. Brown, Richard C. Christian, Helen C. Davies, Jeffrey S. Wells, Timothy Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title_full | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title_fullStr | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title_full_unstemmed | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title_short | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R(1a) activity: evidence for target cell-induced acylation |
title_sort | unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin o-acyl transferase and ghs-r(1a) activity: evidence for target cell-induced acylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374529/ https://www.ncbi.nlm.nih.gov/pubmed/28361877 http://dx.doi.org/10.1038/srep45541 |
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