Understanding the Role of Melanocortin Stimulating Hormone Peptides in Regulation of Obesity

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dc.contributor.advisor Mountjoy, K en
dc.contributor.author Shome, Avik en
dc.date.accessioned 2014-08-08T00:37:20Z en
dc.date.issued 2014 en
dc.identifier.citation 2014 en
dc.identifier.uri http://hdl.handle.net/2292/22675 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract The melanocortin 4 receptor (MC4R) and pro-opiomelanocortin (POMC) are known to play essential roles in body weight regulation. However it is unknown which of the multiple melanocortin peptides derived from POMC are required specifically for body weight regulation. To better understand the physiological roles of two POMC-derived peptides, α-melanocyte stimulating hormone (α-MSH) and desacetyl-α-MSH, the Mountjoy laboratory created an ACTH1-13 null KI mouse that is devoid of both peptides and develops age-onset obesity. The Mountjoy laboratory also showed that central administration of α-MSH or desacetyl-α-MSH and peripheral administration of only α-MSH reduces body weight in male mice. Using the ACTH1-13 null KI mouse, first we show that central administration of β-MSH, which is not normally present in mice, significantly reduces male homozygous mouse body weight; supporting the hypothesis of others that β-MSH could be an endogenous melanocortin peptide regulating human body weight. Second, we show that peripherally administered α-MSH or desacetyl-α-MSH to female homozygous ACTH1-13 null KI mice fails to reduce body weight. However, both peptides appeared to protect the mice from post-operative stress-induced body weight loss. This disproves our hypothesis that females respond similar to males and highlights a gender difference for these mice. Third, we demonstrate non-linear dose-dependent effects of peripheral administration of either α-MSH or desacetyl- α-MSH on male homozygous ACTH1-13 null KI mouse body weight. Furthermore, we show that a dose of 2.5μg desacetyl-α-MSH or 5μg α-MSH significantly reduces male body weight, but a 1:1 ratio treatment using 2.5μg of each peptide did not reduce body weight. This supports our hypothesis and shows that complex opposing interactions occur between α-MSH and desacetyl-α-MSH when administered peripherally in male mice. Fourth, we show using digital droplet PCR that there are significant differences in expression of some adipose-related genes but not in the expression of the FGF21 gene in liver and adipose tissue between wild type and homozygous mice. This appears to disprove our hypothesis that FGF21 and browning of white adipose tissue is a mechanism whereby α-MSH and desacetyl-α-MSH regulate mouse body weight. Overall the ACTH1-13 null KI mouse has proved to be a valuable model in this thesis for advancing the knowledge about the endogenous melanocortin system. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland 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 Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ en
dc.title Understanding the Role of Melanocortin Stimulating Hormone Peptides in Regulation of Obesity en
dc.type Thesis en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The Author en
pubs.elements-id 449004 en
pubs.org-id Academic Services en
pubs.org-id Examinations en
pubs.record-created-at-source-date 2014-08-08 en

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