dc.contributor.author |
Mountjoy, Kathleen |
en |
dc.contributor.author |
Caron, Alexandre |
en |
dc.contributor.author |
Hubbard, Kristina |
en |
dc.contributor.author |
Shome, Avik |
en |
dc.contributor.author |
Grey, Angus |
en |
dc.contributor.author |
Sun, Bo |
en |
dc.contributor.author |
Bould, Sarah |
en |
dc.contributor.author |
Middleditch, Martin |
en |
dc.contributor.author |
Pontré, Beau |
en |
dc.contributor.author |
McGregor, Ailsa |
en |
dc.contributor.author |
Harris, Paul |
en |
dc.contributor.author |
Kowalczyk, Renata |
en |
dc.contributor.author |
Brimble, Margaret |
en |
dc.contributor.author |
Botha, Rikus |
en |
dc.contributor.author |
Tan, Karen ML |
en |
dc.contributor.author |
Piper, Sarah J |
en |
dc.contributor.author |
Buchanan, Christina |
en |
dc.contributor.author |
Lee, Syann |
en |
dc.contributor.author |
Coll, Anthony P |
en |
dc.contributor.author |
Elmquist, Joel K |
en |
dc.date.accessioned |
2019-03-11T20:27:06Z |
en |
dc.date.issued |
2018-03 |
en |
dc.identifier.citation |
Molecular Metabolism 9:207-216 Mar 2018 |
en |
dc.identifier.issn |
2212-8778 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/45892 |
en |
dc.description.abstract |
OBJECTIVE:Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro. Thus, the physiological role for desacetyl-α-MSH is still unclear. METHODS:We created a novel mouse model to determine whether desacetyl-α-MSH plays a role in regulating energy balance. We engineered a knock in targeted QKQR mutation in the POMC protein cleavage site that blocks the production of both desacetyl-α-MSH and α-MSH from adrenocorticotropin (ACTH1-39). RESULTS:The mutant ACTH1-39 (ACTHQKQR) functions similar to native ACTH1-39 (ACTHKKRR) at the melanocortin 2 receptor (MC2R) in vivo and MC4R in vitro. Male and female homozygous mutant ACTH1-39 (Pomctm1/tm1) mice develop the characteristic melanocortin obesity phenotype. Replacement of either desacetyl-α-MSH or α-MSH over 14 days into Pomctm1/tm1 mouse brain significantly reverses excess body weight and fat mass gained compared to wild type (WT) (Pomcwt/wt) mice. Here, we identify both desacetyl-α-MSH and α-MSH peptides as regulators of energy balance and highlight a previously unappreciated physiological role for desacetyl-α-MSH. CONCLUSIONS:Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH. |
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dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Molecular metabolism |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
en |
dc.subject |
Animals |
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dc.subject |
Mice, Inbred BALB C |
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dc.subject |
Mice, Inbred C57BL |
en |
dc.subject |
Mice |
en |
dc.subject |
Weight Gain |
en |
dc.subject |
alpha-MSH |
en |
dc.subject |
Receptor, Melanocortin, Type 2 |
en |
dc.subject |
Receptor, Melanocortin, Type 4 |
en |
dc.subject |
Protein Binding |
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dc.subject |
Energy Metabolism |
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dc.subject |
Mutation |
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dc.subject |
Female |
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dc.subject |
Male |
en |
dc.subject |
Proteolysis |
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dc.title |
Desacetyl-α-melanocyte stimulating hormone and α-melanocyte stimulating hormone are required to regulate energy balance. |
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dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.molmet.2017.11.008 |
en |
pubs.begin-page |
207 |
en |
pubs.volume |
9 |
en |
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
29226825 |
en |
pubs.end-page |
216 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
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pubs.subtype |
brief-report |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
Journal Article |
en |
pubs.subtype |
Research Support, N.I.H., Extramural |
en |
pubs.elements-id |
719697 |
en |
pubs.org-id |
Academic Services |
en |
pubs.org-id |
Examinations |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
en |
pubs.org-id |
Physiology Division |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Chemistry |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
2212-8778 |
en |
pubs.record-created-at-source-date |
2017-12-12 |
en |
pubs.dimensions-id |
29226825 |
en |