title: Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1aactivity: evidence for target cell-induced acylation.
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.
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Hopkins
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Timothy A S
authors.initials: TA
authors.lastname: Nelson
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Guschina
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Parsons
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Lewis
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Brown
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.affiliation: Institute of Life Science, School of Medicine, Swansea University, Swansea, SA2 8PP, UK.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Davies
authors.affiliation: Neuroscience &Mental Health Research Institute, and School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wells
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002849:Chromatography, Gas; D054439:Ghrelin / Q000378:metabolism*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D054440:Receptors, Ghrelin / Q000172:deficiency / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; D054440:Receptors, Ghrelin; D000217:Acyltransferases; C526983:Mboat4 protein, mouse