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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6164918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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