Endocrine Abstracts

Obesity is a polymorphic chronic disease with epidemic prevalence. Furthermore, heritability of the weight phenotype is high. However, within the catabolic leptin–melanocortin signalling pathway, which is pivotal for body weight regulation, gene mutations are rare. This indicates that other, non-genetic heritable factors might play a role in the development of obesity, such as epigenetic mechanisms.

In a candidate gene approach, we analyzed the functional relevance and ontogenesis of the DNA methylation of the proopiomelanocortin (POMC) gene, which has a key role in hypothalamic body weight regulation. In vitro luciferase reporter gene analyses revealed DNA methylation-dependent promoter activity of both CpG islands (CGIs) of POMC. Regarding the ontogenesis, postnatally stable POMC DNA methylation patterns with interindividual conservation and non-tissue specificity were detected for both CGIs in mice, applying bisulfite sequencing. In addition, it was observed that the POMC DNA methylation patterns develop prenatally between the blastocystal stage and the early organogenesis.

Overall, these results indicate that stochastic variances arising in the course of the POMC DNA methylation development might influence the POMC activity and consequently alter the risk to develop obesity.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.