Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for b-MSH and desacetyl a-MSH in energy homeostasis
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Otros documentos de la autoría: Kirwan, Peter; Kay, Richard G.; Brouwers, Bas; Herranz-Pérez, Vicente; Jura, Magdalena; Larraufie, Pierre; Jerber, Julie; Pembroke, Jason; Bartels, Theresa; White, Anne; Gribble, Fiona M.; Reimann, Frank; Farooqi, I. Sadaf; O’Rahilly, Stephen; Merkle, Florian
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INVESTIGACIONMetadatos
Título
Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for b-MSH and desacetyl a-MSH in energy homeostasisAutoría
Fecha de publicación
2018Editor
ElsevierISSN
2212-8778Cita bibliográfica
KIRWAN, Peter, et al. Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis. Molecular metabolism, 2018, vol. 17, p. 82-97.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://www.sciencedirect.com/science/article/pii/S2212877818305325#!Versión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both
humans and rodents that is treatable with synthetic melanocortins. However, there ... [+]
Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both
humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between
humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study
was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their
production is dynamically regulated.
Methods: We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from human pluripotent stem
cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the sequence and quantify the production of
hypothalamic neuropeptides, including those derived from POMC.
Results: In both in vitro and in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of neuropeptides as a resource for the
field. Although the existence of b-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl a-MSH
(d-a-MSH) were produced in considerable excess of acetylated a-MSH. In hPSC-derived hypothalamic neurons, these POMC derivatives were
appropriately trafficked, secreted, and their production was significantly (P < 0.0001) increased in response to the hormone leptin.
Conclusions: Our findings challenge the assumed pre-eminence of a-MSH and suggest that in humans, d-a-MSH and b-MSH are likely to be
the predominant physiological products acting on melanocortin receptors. [-]
Publicado en
Molecular Metabolism, Volume 17, November 2018.Proyecto de investigación
SBF001\1016 ; MR/P501967/1 ; MR/M009041/1 ; 4050281695 ; MC UU 12012/3 ; MC UU 12012/5 ; 106262/Z/14/Z ; 106263/Z/14/Z ; PSAG/097 ; PROMETEOII/2014/075 ; OTAR0039 ; RD16/0011/0026Derechos de acceso
info:eu-repo/semantics/openAccess
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