Increased POMC Methylation Linked to Severe Obesity Risk in New Study

Researchers from Charité–Universitätsmedizin Berlin have linked increased methylation of the POMC gene to an increased risk of developing severe obesity, especially among women, but say that medication may be able to help with weight loss. In Science Translational Medicine, the researchers analyzed POMC methylation in blood samples from 1,128 individuals — the POMC gene encodes the protein proopiomelanocortin, which regulates satiety as part of the leptin-melanocortin signaling pathway — to find increased POMC methylation was associated with a 1.4-fold increased risk of obesity among women. They further found in additional analyses using human stem cell-derived POMC-expressing hypothalamic neurons that increased POMC methylation is linked to decreased POMC gene expression, and that that methylation pattern is set early in embryonic development. Based on these findings, the researchers treated five individuals with obesity who had highly methylated POMC genes with an MC4R agonist — the MC4R agonist setmelanotide is approved in the US for patients with POMC and other gene mutations — to find that those individuals lost weight. "These findings show, for a start, that a POMC gene that has undergone epigenetic changes can in fact potentially be addressed through medication," senior author Peter Kühnen from Charité says in a statement.