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Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a 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. and Wells, Timothy 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: Biosciences
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > Q Science (General)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 1 March 2017
Date of Acceptance: 21 February 2017
Last Modified: 24 May 2020 15:18
URI: http://orca.cf.ac.uk/id/eprint/98667

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