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Published on: September 11, 2018
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Loss of Imprinting of
Mathew Van de Pette1, Simon J Tunster2, Rosalind M John3
1School of BioSciences, Cardiff University, Cardiff CF10 3AX, UK. matthew.van-de-pette@imperial.ac.uk.
International Journal of Molecular Sciences
|September 15, 2018
Summary
Altering the expression of Cyclin dependent kinase inhibitor 1c (Cdkn1c) protects against obesity and metabolic issues. Modest increases in Cdkn1c guard against age-related weight gain and diet-induced obesity.
Area of Science:
- Genetics
- Metabolism
- Developmental Biology
Background:
- Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted gene.
- Cdkn1c plays roles in embryonic development, metabolism, and behavior.
- Previous studies linked Cdkn1c to brown adipose tissue formation.
Purpose of the Study:
- To model the loss of imprinting of Cdkn1c in adult mice.
- To investigate the protective effects of altered Cdkn1c expression against metabolic dysfunction.
- To examine the stability of Cdkn1c imprinting in aged and diet-challenged adipose tissue.
Main Methods:
- Utilized transgenic mouse models with altered Cdkn1c dosages.
- Assessed protection against age-related weight gain, glucose intolerance, and insulin intolerance.
- Performed bisulphite sequencing to analyze differentially methylated regions regulating Cdkn1c imprinting.
Main Results:
- A two-fold increase in Cdkn1c expression during development protected against age-related weight gain and metabolic intolerance.
- Loss of imprinting of Cdkn1c conferred protection against diet-induced obesity.
- Differentially methylated regions remained unaltered in aged or diet-challenged adipose tissue despite reduced Cdkn1c expression.
- A natural decline in Cdkn1c expression was observed with aging, potentially contributing to metabolic decline.
Conclusions:
- Cdkn1c plays a critical role in regulating adult adipose tissue.
- Modest changes in Cdkn1c expression can protect against obesity and metabolic syndrome.
- The decline in Cdkn1c expression with age may impact metabolic health.
- Post-natal imprinting is insensitive to environmental factors, unlike in utero imprinting.
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