Effect of altered Cdkn1c dosage in adipose tissue

Van De Pette, Mathew 2012. Effect of altered Cdkn1c dosage in adipose tissue. PhD Thesis, Cardiff University. Item availability restricted.

Preview	PDF Download (12MB) | Preview
	PDF - Additional Metadata Restricted to Repository staff only Download (415kB)

Abstract

Genomic imprinting is an epigenetic process in which the instructions for gene activation or gene silencing are initiated in the germline by DNA methylation. Many imprinted genes play key roles regulating fetal growth and placental development. In addition to their prenatal roles, several imprinted genes have been shown to play significant roles postnatally in particularly with respect to regulating behaviour and metabolism. Cdkn1c, a maternally expressed imprinted gene, codes for the p57Kip2 protein which is a cyclin dependent kinase inhibitor, belonging to the same CIP/KIP family as p21 and p27. Cdkn1c was shown to be expressed and imprinted in a small population of cells within post natal iBAT and rWAT. Using both loss-of-function and gain-in-expression models, a critical and dosage-related function for Cdkn1c in brown adipogenesis was identified, through Prdm16 and C/ebpβ. Consistent with an increase in mitochondrial uncoupling, mice that over-expressed Cdkn1c were found to be protected against diet- and age-induced obesity, in a dosage dependent manner. Cdkn1c may therefore represent a novel route towards obesity therapy and corroborates the hypothesis that the brown adipose tissue may represent a key area of genomic conflict in mammals.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > QR Microbiology
Funders:	BBSRC
Last Modified:	19 Mar 2016 23:13
URI:	https://orca.cardiff.ac.uk/id/eprint/43525

Actions (repository staff only)

Edit Item