Leptin supplementation of neonatal rats during the suckling period protects against being
overweight in adulthood and ameliorates the control of food intake. This was associated with changes in the expression of hypothalamic genes involved in the central action of
leptin:
pro-opiomelanocortin (
Pomc),
leptin receptor (Lepr) and suppressor of
cytokine signalling (Socs3). The purpose of the present study was to determine the methylation status within the promoter regions of these genes and to assess whether the observed changes in the expression levels of these genes could be explained by changes in their methylation status. Male rats were treated daily with an oral physiological dose of
leptin or vehicle during the suckling period. After weaning, animals were fed with a normal-fat or a high-fat (HF) diet until aged 6 months.
DNA was extracted from the hypothalamus and methylation within the promoter regions of the gene panel was measured by pyrosequencing.
Pomc promoter methylation increased in control animals fed the HF diet but decreased in
leptin-treated animals. In addition, there was a weak negative correlation between DNA methylation and
POMC mRNA levels (P = 0·075). There were no changes in the methylation status of the CpG sites studied within the promoter regions of Lepr and Socs3 in response to
leptin or HF treatments. This is the first demonstration that
leptin treatment during lactation may programme methylation of an appetite-related gene in the hypothalamus of animals fed HF diets, with possible implications for gene expression and protection against the development of
obesity.