Academic Journal
Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation
| العنوان: | Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation |
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| المؤلفون: | Hopkins, A, Nelson, T, Guschina, I, Parsons, L, Lewis, C, Brown, R, Christian, H, Davies, J, Wells, T |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2017 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://ora.ox.ac.uk/objects/uuid:0d64e3a0-166e-48a9-b7b4-760cd9c98419; https://doi.org/10.1038/srep45541 |
| DOI: | 10.1038/srep45541 |
| الاتاحة: | https://doi.org/10.1038/srep45541 https://ora.ox.ac.uk/objects/uuid:0d64e3a0-166e-48a9-b7b4-760cd9c98419 |
| Rights: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.FA7DD38F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/srep45541 |
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