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. and Wells, Timothy  ORCID: https://orcid.org/0000-0003-3618-0595
2017.
Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target-cell-induced acylation.
Scientific Reports
7
, 45541.
10.1038/srep45541
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Abstract
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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences Schools > Medicine Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) |
| Subjects: | Q Science > Q Science (General) |
| Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. |
| Publisher: | Nature Publishing Group |
| ISSN: | 2045-2322 |
| Date of First Compliant Deposit: | 1 March 2017 |
| Date of Acceptance: | 21 February 2017 |
| Last Modified: | 25 Oct 2023 01:06 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/98667 |
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