Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 OC1.2

Diabetes and metabolism

Moderate maternal undernutrition results in epigenetic changes in the fetal hypothalamic feeding centres, but not in the fetal HPA axis

Ghazala Begum1, Adam Stevens1, Mark Oliver3, Kristin Connor3, John Challis2, Frank Bloomfield3 & Anne White1

1University of Manchester, Manchester, UK; 2University of Toronto, Toronto, Canada; 3University of Auckland, Auckland, New Zealand.

Maternal undernutrition influences the development of obesity and diabetes in the adult offspring. Previous work has shown that moderate maternal undernutrition may alter the stress–response of the hypothalamic–pituitary–adrenal (HPA) axis; however, it is not clear if this is the mechanism for consequent obesity in offspring.

The aim of this study was to analyse epigenetic changes in the POMC and GR genes in the pituitary as markers of HPA axis activity and compare these to other brain regions.

For this work a sheep model of periconceptional undernutrition was used. Ewes were undernourished (UN, n=6) for 60 days pre- and 30 days post-mating or given normal feed (N, n=6). Brain tissues (ventral hypothalami, hippocampi and pituitaries) were dissected at post mortem (day 135). POMC and GR mRNA expression and promoter region methylation were assessed.

In the stress axis there was no evidence of changes in promoter methylation and expression of the GR and POMC genes in the fetal hippocampus and anterior pituitary. In the fetal circulation there were no changes in POMC, ACTH or cortisol concentrations. In comparison, in the hypothalamic feeding centres POMC and GR gene promoter methylation were decreased in the offspring from the UN group (62 and 53% decrease respectively) and GR gene mRNA expression was increased (4.7-fold).

In summary, following maternal periconceptional undernutrition there is no evidence for epigenetic changes in stress axis genes in the fetal hippocampus and pituitary. In contrast, significant changes were observed in promoter methylation of POMC and GR genes in hypothalamic feeding centres. These observations suggest that fetal programming of the ventral hypothalamus may be involved in the development of obesity in adult offspring but similar changes were not found in the stress axis.

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