Chronic High-Fat Diet Exacerbates Sexually Dimorphic Pomctm1/tm1 Mouse Obesity.

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dc.contributor.author Hubbard, Kristina en
dc.contributor.author Shome, Avik en
dc.contributor.author Sun, Bo en
dc.contributor.author Pontré, Beau en
dc.contributor.author McGregor, Ailsa en
dc.contributor.author Mountjoy, Kathleen en
dc.date.accessioned 2020-02-17T22:18:54Z en
dc.date.issued 2019-05 en
dc.identifier.citation Endocrinology 160(5):1081-1096 May 2019 en
dc.identifier.issn 0013-7227 en
dc.identifier.uri http://hdl.handle.net/2292/50091 en
dc.description.abstract Mice with a targeted mutation in the pro-opiomelanocortin (Pomc) gene (Pomctm1/tm1 mice) are unable to synthesize desacetyl-α-MSH and α-MSH and they develop obesity when fed chow diet. In this study, we hypothesized that a chronic high-fat (HF) diet exacerbates Pomctm1/tm1 mouse obesity. Male and female Pomcwt/wt and Pomctm1/tm1 mice were fed low-fat (LF) (10 kcal percent fat) or HF (45 kcal percent fat) diets from weaning for 23 weeks. We show that Pomctm1/tm1 mouse obesity is sexually dimorphic and exacerbated by an HF diet. Male Pomctm1/tm1 mice develop obesity because they are hyperphagic compared with Pomcwt/wt mice when fed an LF or HF diet. Female Pomctm1/tm1 mice develop obesity when feeding on an LF or HF diet because they exhibit signs of reduced energy expenditure (no change in feed efficiency; body weight gained exceeding energy intake) compared with Pomcwt/wt mice. A chronic HF diet exacerbates male Pomctm1/tm1 and Pomcwt/wt mouse obesity, and the increased energy intake fully accounts for increased weight gain. In contrast, female Pomcwt/wt mice are protected from chronic HF diet-induced obesity because they reduce the amount of HF diet eaten, and they appear to increase their energy expenditure (no change in feed efficiency but energy intake exceeding body weight gained). A chronic HF diet exacerbates female Pomctm1/tm1 mouse obesity due to impaired ability to reduce the amount of HF diet eaten and apparent impaired HF diet-induced adaptive thermogenesis. Our data show that desacetyl-α-MSH and α-MSH are required for sexually dimorphic HF diet-induced C57BL/6J obesity. In conclusion, desacetyl-α-MSH and α-MSH play salutary roles in sexually dimorphic melanocortin obesity and sexually dimorphic HF diet-induced C57BL/6J obesity. en
dc.format.medium Print en
dc.language eng en
dc.relation.ispartofseries Endocrinology 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 en
dc.subject Mice, Inbred C57BL en
dc.subject Obesity en
dc.subject Weight Gain en
dc.subject Pro-Opiomelanocortin en
dc.subject alpha-MSH en
dc.subject Dietary Fats en
dc.subject Sex Factors en
dc.subject Energy Metabolism en
dc.subject Energy Intake en
dc.subject Thermogenesis en
dc.subject Mutation en
dc.subject Female en
dc.subject Male en
dc.subject Diet, High-Fat en
dc.title Chronic High-Fat Diet Exacerbates Sexually Dimorphic Pomctm1/tm1 Mouse Obesity. en
dc.type Journal Article en
dc.identifier.doi 10.1210/en.2018-00924 en
pubs.issue 5 en
pubs.begin-page 1081 en
pubs.volume 160 en
dc.rights.holder Copyright: Endocrine Society en
pubs.end-page 1096 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 772835 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 Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1945-7170 en
pubs.record-created-at-source-date 2019-04-19 en
pubs.dimensions-id 30997487 en


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https://creativecommons.org/licenses/by/4.0/ Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/

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