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Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity

Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting brown adipose tissue form...

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Autores principales: Van de Pette, Mathew, Tunster, Simon J., John, Rosalind M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164918/
https://www.ncbi.nlm.nih.gov/pubmed/30213134
http://dx.doi.org/10.3390/ijms19092734
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author Van de Pette, Mathew
Tunster, Simon J.
John, Rosalind M.
author_facet Van de Pette, Mathew
Tunster, Simon J.
John, Rosalind M.
author_sort Van de Pette, Mathew
collection PubMed
description Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting brown adipose tissue formation. Here, we use these transgenic mouse lines to model the loss of imprinting of Cdkn1c in adulthood. We demonstrate that only a two-fold increase in the expression of Cdkn1c during development is sufficient to protect against age-related weight gain in addition to glucose and insulin intolerance. Further to this, we show that the loss of imprinting of Cdkn1c protects against diet-induced obesity. Bisulphite sequencing was performed to test the stability of the two differentially methylated regions that regulate Cdkn1c imprinting, and both were found to be unaltered in aged or diet-challenged adipose tissue, despite drastic reductions in Cdkn1c expression. These data demonstrate a critical role for Cdkn1c in regulating adult adipose tissue, with modest changes in expression capable of protecting against both age and diet-induced obesity and metabolic syndrome, with a natural decline in Cdkn1c expression observed that may contribute to less healthy metabolic aging. Finally, we have observed a post-natal insensitivity of the imprint to environmental factors, in contrast to recent observations of an in utero sensitivity.
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spelling pubmed-61649182018-10-10 Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity Van de Pette, Mathew Tunster, Simon J. John, Rosalind M. Int J Mol Sci Article Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene with roles in embryonic development, post-natal metabolism and behaviour. Using mouse models with altered dosages of Cdkn1c, we have previously identified a role for the gene in promoting brown adipose tissue formation. Here, we use these transgenic mouse lines to model the loss of imprinting of Cdkn1c in adulthood. We demonstrate that only a two-fold increase in the expression of Cdkn1c during development is sufficient to protect against age-related weight gain in addition to glucose and insulin intolerance. Further to this, we show that the loss of imprinting of Cdkn1c protects against diet-induced obesity. Bisulphite sequencing was performed to test the stability of the two differentially methylated regions that regulate Cdkn1c imprinting, and both were found to be unaltered in aged or diet-challenged adipose tissue, despite drastic reductions in Cdkn1c expression. These data demonstrate a critical role for Cdkn1c in regulating adult adipose tissue, with modest changes in expression capable of protecting against both age and diet-induced obesity and metabolic syndrome, with a natural decline in Cdkn1c expression observed that may contribute to less healthy metabolic aging. Finally, we have observed a post-natal insensitivity of the imprint to environmental factors, in contrast to recent observations of an in utero sensitivity. MDPI 2018-09-12 /pmc/articles/PMC6164918/ /pubmed/30213134 http://dx.doi.org/10.3390/ijms19092734 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Van de Pette, Mathew
Tunster, Simon J.
John, Rosalind M.
Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title_full Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title_fullStr Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title_full_unstemmed Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title_short Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity
title_sort loss of imprinting of cdkn1c protects against age and diet-induced obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164918/
https://www.ncbi.nlm.nih.gov/pubmed/30213134
http://dx.doi.org/10.3390/ijms19092734
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