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Risk markers for obesity

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Charité researchers decode epigenetic variant

Researchers at Charité – Universitätsmedizin Berlin have been able to show with research groups in London (UK) and Houston (USA) that the risk of developing certain disorders, such as obesity, is tied to more than purely genetic factors. Changes affecting modifications of the cell's genetic material can also contribute to disease development. The researchers found that an epigenetic variant in the POMC gene, which plays a significant role in controlling body weight, is associated with an increased lifetime risk of developing obesity. Results from this study have been published in the journal Cell Metabolism*.

Studies involving identical twins suggest that regulation of body weight is heavily influenced by genetics. However, genetic variants so far identified as being involved in body weight regulation only explain a small percentage of this genetic contribution. “This is why we decided to ask whether, in addition to genetic variants, epigenetic changes might also play a role in the regulation body weight,” explains Dr. Peter Kühnen, a researcher from the Institute of Experimental Pediatric Endocrinology. The term epigenetics refers to the action of variants, which are capable of regulating gene function without changing the sequence of the relevant gene(s). 'DNA methylation' is probably the most stable type of epigenetic change.

“Our study has shown that both, obese children and obese adults, show higher rates of increased methylation activity in a specific section of the POMC gene compared to normal weight individuals,” says Dr. Kühnen. He adds: “We were also able to identify the same methylation variant in POMC neurons in the brains of deceased obese persons.” After detecting this variant in the blood cells of newborn babies, the endocrinologist's research team was able to show that POMC methylation remained stable during the first years of life. During their investigation of POMC methylation in children, the researchers were also able to observe a paternal effect. Changes in the gene responsible for regulating body weight appear to lead to an increased risk of developing obesity.

However, the epigenetic variant investigated as part of this study is not the main cause of obesity; it is merely one of many potential contributing factors. As a next step, the researchers will attempt to understand how this epigenetic variant of the POMC gene develops, and what might explain the paternal influence on the DNA methylation patterns observed in children.

*Kühnen P, Handke D, Waterland RA, Hennig BJ, Silver M, Fulford AJ, Dominguez-Salas P, Moore SE, Prentice AM, Spranger J, Hinney A, Hebebrand J, Heppner FL, Walzer L, Grötzinger C, Gromoll J, Wiegand S, Grüters A, Krude H. Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity. Cell Metabolism, 2016 Sep 13; 24(3):502-9. doi: 10.1016/j.cmet.2016.08.001.


Institute of Experimental Pediatric Endocrinology


Dr. Peter Kühnen
Institute of Experimental Pediatric Endocrinology
Charité – Universitätsmedizin Berlin
Tel: +49 30 450 666 839

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