SFEBES2009 Poster Presentations Diabetes, Metabolism and Cardiovascular (49 abstracts)
Periconceptional undernutrition is associated with epigenetic changes in the Proopiomelanocortin (POMC) gene in the hypothalamus of foetal sheep
A Stevens 1 , A Cook 1 , C Rumball 2 , M Oliver 2 , K Connor 3 , J Challis 3 , F Bloomfield 2 & A White 1
1University of Manchester, Manchester, UK; 2The Liggins Institute, University of Auckland, Auckland, New Zealand; 3University of Toronto, Toronto, Canada.
Maternal undernutrition influences the development of diseases such as obesity and diabetes in the adult offspring. Programming of key genes involved in hypothalamic appetite regulation such as proopiomelanocortin (POMC) and neuropeptide Y (NPY) may affect energy balance in adulthood. These changes may occur by alterations in gene expression or epigenetic changes including histone acetylation and DNA methylation. This study aims to examine the effects of maternal undernutrition on POMC and NPY as key appetite regulatory neuropeptides in the foetal sheep hypothalamus.
Using a model of periconceptional undernutrition, ewes were undernourished (UN, n=4) for 30 days pre- and 60 days post-mating or given normal feed (N, n=4). Hypothalami were dissected at post mortem (day 135) and the arcuate nucleus selected. POMC and NPY mRNA expression assessed by quantitative expression analysis (Quantigene, Panomics) remained unchanged between the two groups. POMC gene analysis by methylation PCR revealed hypomethylation in the UN group (64% decrease, P=0.001).
To investigate these observations further, the ventral hypothalamus (enriched for the arcuate nucleus) was taken from a replicate experiment (UN, n=11; N, n=9). Again, marked hypomethylation of the POMC gene was found in the UN group (61.6% decrease, P=0.0003), with no change in POMC or NPY mRNA expression. Transcriptional activation of the POMC gene was investigated using ChIP to examine histone H3K9 acetylation using rabbit polyclonal antibody, AB 12178. This revealed increased H3K9 acetylation of the POMC gene in the UN group (1.63 fold increase, P=0.0003).
Therefore, although hypothalamic POMC expression is unchanged in the UN foetal sheep, presence of hypomethylation and histone H3K9 acetylation is evidence of epigenetic changes. This suggests that there may be foetal programming of the hypothalamic appetite regulatory system, predisposing to obesity in adults.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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