Obese people are at increased risk of several serious diseases, such as cardiovascular disease, diabetes, and cancer. It is a growing health issue. The number of overweight people is increasing throughout the world. 2 out of 3 adults (59 percent) in Europe are overweight or obese, according to the World Health Organization (
But what decides whether people will become obese? Genetic factors play a major role, along with lifestyle. The similarity of the body mass index (BMI) in identical twins ranges from 40 to 70 percent. Even when raised in different families, they show the same significant similarity.
Obesity May Be Caused by the ‘Hunger Gene’
Scientists have identified several genetic variants that influence a person’s body weight. But all these things cannot explain the heritability that has been observed. Researchers started to suspect there must be additional non-genetic factors that influence weight gain.
Researchers have now identified one such factor. According to their findings, women’s risk of gaining excess weight increases by about 44 percent if excess methyl groups adhere to the POMC (pro-opiomelanocortin) gene, which is responsible for the feeling of satiety.
Methyl groups are tiny chemical units that activate or deactivate genes without modifying the sequence of letters in the DNA. This type of “DNA formatting” is known as epigenetic marking.
For their study, researchers analyzed the “formatting” of the POMC gene in more than 1,100 people. They found more methyl groups attached to the gene in obese women with a BMI of over 35 compared to normal body weight (2✔ ✔Trusted Source
Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice
Go to source).
Researchers compared methylation patterns in more than 15 sets of identical and fraternal twins to show that the POMC gene is “formatted” very early on during embryonic development. While the “formatting” was the same in most of the identical twins, there was hardly any similarity in the fraternal twins.
This indicates that the epigenetic marking of the POMC gene is established shortly after the egg and sperm cells merge before the fertilized egg divides into two twin embryos. Hence, the very early stage of pregnancy is important for obesity risk.
New Anti-Obesity Drug Arising from Knowledge of Genetic Obesity Traits
Past studies indicated that the presence or absence of certain nutrients that supply methyl groups could influence this process. These nutrients, including betaine, methionine, and folic acid are absorbed through a person’s diet.
A newly developed method involving individual human stem cells allowed researchers to simulate in the lab how the methylation pattern is determined during embryonic development and how nutrients influence it.
They observed that the ‘DNA formatting system’ is very stable, with cells compensating for minor fluctuations in the nutrient supply. On the other hand, there are indications that the variability of this ‘formatting’ develops randomly.
At least, researchers speculated that women who are at elevated risk of developing obesity due to methylation of the POMC gene could receive medications to help them lose weight. The subjects were given a specific drug that stops the hunger feeling and has already been approved to treat obese patients with a mutation of the POMC gene (3✔ ✔Trusted Source
Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment
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Within three months after starting treatment, all five patients experienced less hunger. They lost an average of seven kilograms or about five percent of their body weight. Some of them continued the treatment and continued to lose weight.
These findings show that the satiety gene undergone epigenetic changes can be potentially addressed through medication. Further large controlled studies will be needed to show whether treatment is effective and safe over a longer period. Still, this medication would be just one piece of a holistic treatment strategy.
- The Hunger Genes: Pathways to Obesity – (https://www.cell.com/cell/fulltext/S0092-8674(15)00261-5)
- Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice – (https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.0020081)
- Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment – (https://www.science.org/doi/10.1126/scitranslmed.adg1659)
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