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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

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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

dc.contributor.author	Kirwan, Peter
dc.contributor.author	Kay, Richard G.
dc.contributor.author	Brouwers, Bas
dc.contributor.author	Herranz Pérez, Vicente
dc.contributor.author	Jura, Magdalena
dc.contributor.author	Larraufie, Pierre
dc.contributor.author	Jerber, Julie
dc.contributor.author	Pembroke, Jason
dc.contributor.author	Bartels, Theresa
dc.contributor.author	White, Anne
dc.contributor.author	Gribble, Fiona M.
dc.contributor.author	Reimann, Frank
dc.contributor.author	Farooqi, I. Sadaf
dc.contributor.author	O'Rahilly, Stephen
dc.contributor.author	Merkle, Florian T.
dc.date.accessioned	2022-04-07T14:20:48Z
dc.date.available	2022-04-07T14:20:48Z
dc.date.issued	2018
dc.identifier.citation	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 T. 2018 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 17 82 97
dc.identifier.uri	https://hdl.handle.net/10550/82226
dc.description.abstract	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 β-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl α-MSH (d-α-MSH) were produced in considerable excess of acetylated α-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 α-MSH and suggest that in humans, d-α-MSH and β-MSH are likely to be the predominant physiological products acting on melanocortin receptors.
dc.language.iso	eng
dc.relation.ispartof	Molecular Metabolism, 2018, vol. 17, p. 82-97
dc.subject	Obesitat
dc.subject	Pèptids
dc.title	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
dc.type	journal article	es_ES
dc.date.updated	2022-04-07T14:20:48Z
dc.identifier.doi	10.1016/j.molmet.2018.08.006
dc.identifier.idgrec	151253
dc.rights.accessRights	open access	es_ES