Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol

Novoselova, Tatiana ORCID: https://orcid.org/0000-0002-2394-4667, Larder, Rachel, Rimmington, Debra, Lelliot, Christopher, Wynn, Elizabeth, Gorrigan, Rebecca, Tate, Path, Guasti, Leonardo, Sanger Mouse Genetics Project, The, O'Rahilly, Stephen, Clark, Adrian, Logan, Darren, Coll, Anthony and Chan, Li F. (2016) Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol. Journal of Endocrinology, 230 (1) . pp. 13-26. ISSN 0022-0795 [Article] (doi:10.1530/JOE-16-0057)

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Abstract

Melanocortin receptor accessory protein 2 (MRAP2) is a transmembrane accessory protein predominantly expressed in the brain. Both global and brain-specific deletion of Mrap2 in mice results in severe obesity. Loss-of-function MRAP2 mutations have also been associated with obesity in humans. Although MRAP2 has been shown to interact with MC4R, a G protein-coupled receptor with an established role in energy homeostasis, appetite regulation and lipid metabolism, the mechanisms through which loss of MRAP2 causes obesity remains uncertain. In this study, we used two independently derived lines of Mrap2 deficient mice (Mrap2tm1a/tm1a) to further study the role of Mrap2 in the regulation of energy balance and peripheral lipid metabolism. Mrap2tm1a/tm1a mice have a significant increase in body weight, with increased fat and lean mass, but without detectable changes in food intake or energy expenditure. Transcriptomic analysis showed significantly decreased expression of Sim1, Trh, Oxt and Crh within the hypothalamic paraventricular nucleus of Mrap2tm1a/tm1a mice. Circulating levels of both high-density lipoprotein and low-density lipoprotein were significantly increased in Mrap2 deficient mice. Taken together, these data corroborate the role of MRAP2 in metabolic regulation and indicate that, at least in part, this may be due to defective central melanocortin signalling

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 28129
Notes on copyright: © 2016 Society for Endocrinology. Printed in Great Britain. Published by Bioscientifica Ltd.
This work is licensed under a Creative Commons Attribution 3.0 Unported License
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Depositing User: Tatiana Novoselova
Date Deposited: 12 Nov 2019 12:33
Last Modified: 20 Aug 2020 22:08
URI: https://eprints.mdx.ac.uk/id/eprint/28129

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