Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity.
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Authors
Van de Pette, Mathew
Tunster, Simon J
John, Rosalind M
Publication Date
2018-09-12Journal Title
International Journal of Molecular Sciences
ISSN
1422-0067
Publisher
MDPI AG
Volume
19
Issue
9
Language
eng
Type
Article
This Version
VoR
Metadata
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Van de Pette, M., Tunster, S. J., & John, R. M. (2018). Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity.. International Journal of Molecular Sciences, 19 (9) https://doi.org/10.3390/ijms19092734
Abstract
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.
Keywords
BACs, Cdkn1c, adipose, aging, high fat diet, imprinting, methylation, Aging, Animals, Chromosomes, Artificial, Bacterial, Cyclin-Dependent Kinase Inhibitor p57, Diet, High-Fat, Female, Genomic Imprinting, Male, Mice, Obesity
Sponsorship
M.V.d.P. was supported by a BBSRC DTG studentship BB/F016557. S.J.T. was supported by BBSRC project grant BB/J015156 awarded to R.M.J.
Identifiers
External DOI: https://doi.org/10.3390/ijms19092734
This record's URL: https://www.repository.cam.ac.uk/handle/1810/292715
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