British Journal of Nutrition

Behaviour, Appetite and Obesity

Protective effects of leptin during the suckling period against later obesity may be associated with changes in promoter methylation of the hypothalamic pro-opiomelanocortin gene

M. Paloua1a2, Catalina Picóa1a2 c1, J. A. McKaya3, J. Sáncheza1a2, T. Priegoa1a2, J. C. Mathersa3 and A. Paloua1a2

a1 Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics), University of the Balearic Islands (UIB), Carretera Valldemossa Km 7.5, Palma de Mallorca 07122, Spain

a2 CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma de Mallorca, Spain

a3 Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK


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.

(Received October 07 2010)

(Revised January 19 2011)

(Accepted February 02 2011)

(Online publication May 04 2011)


c1 Corresponding author: Dr C. Picó, fax +34 971173426, email


Abbreviations: HF, high fat; LepR, leptin receptor; NF, normal fat; POMC, pro-opiomelanocortin; SOCS3, suppressor of cytokine signalling 3