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Int. J. Mol. Sci. 2018, 19(9), 2734;

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

School of BioSciences, Cardiff University, Cardiff CF10 3AX, UK
Current address: MRC London Institute of Clinical Sciences, Hammersmith Hospital, London W12 0NN, UK.
Author to whom correspondence should be addressed.
Received: 26 July 2018 / Revised: 6 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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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. View Full-Text
Keywords: Cdkn1c; imprinting; BACs; adipose; aging; high fat diet; methylation Cdkn1c; imprinting; BACs; adipose; aging; high fat diet; methylation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Van de Pette, M.; Tunster, S.J.; John, R.M. Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity. Int. J. Mol. Sci. 2018, 19, 2734.

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