Heredity plays an important role in how prone or not we are to being overweight.
In recent years, researchers have extensively examined which genes and gene variants play a role in this, and have identified approximately one hundred obesity-predisposing genes.
However, genome-wide association studies have shown that less than half of all cases of hereditary obesity can be explained by these genes. The other half is the result of factors that, although part of our DNA, are not genes in the classical sense, he writes EurekAlert.
A group of researchers led by Professor Markus Stoffel from the Department of Biology has now identified another genetic risk factor for hereditary obesity: an endogenous microRNA molecule known as microRNA-7.
Like genes, the blueprints of microRNA molecules are part of chromosomes. But while genes act as building instructions for proteins, the information contained in microRNAs is not translated into proteins.
Is a molecule to blame for obesity?
Instead, microRNA molecules act in our cells as RNA. “MicroRNA-7 is the first microRNA for which we have been able to demonstrate an association with obesity,” says Stoffel.
Together with his team, Stoffel bred mice in which microRNA-7 was missing from certain nerve cells in the hypothalamus, the control center between the endocrine system and the nervous system. These mice demonstrated a pathologically increased appetite and became obese.
ETH researchers were able to demonstrate such a connection in humans as well. Together with scientists from the University of Cambridge, they analyzed genomic and medical data, including the anonymized data held in a British database on 500,000 people.
This allowed Stoffel and his colleagues to demonstrate, in the study published in Nature Communicationsthat people with genetic variations on chromosomes close to the blueprint for microRNA-7 are heavier and taller than average.
How does microRNA-7 work?
The consequence of these genetic variations is that the aforementioned nerve cells of affected individuals produce less microRNA-7.
The scientists were also able to demonstrate that, in these cells, microRNA-7 affects a biochemical pathway known to play a key role in maintaining the body’s energy balance, regulating appetite and controlling the production of growth hormones. MicroRNA acts there by regulating protein production.
It was no surprise to Stoffel that this effect could be seen in both mice and humans. As he points out, microRNA-7 is a molecule that appeared very early in the evolutionary history of the animal kingdom and has survived to the present day. It persists unchanged in many animal species.
“Until now, it was not clear why genetic variations could only explain less than half of the causes of hereditary obesity,” says Stoffel.
The new discoveries could also be used in medicine
“Our study now shows that it is not enough to look for the answer only in the genes that encode information for proteins. Parts of DNA outside genes, such as regions containing the blueprints for microRNAs, must also be examined.”
At least in theory, these new discoveries could also be used in medicine. There are already RNA-based drugs that use the mechanisms of action of microRNA molecules in the body.
One day it may be possible to develop a treatment for people who are obese as a result of their hypothalamus producing insufficient amounts of microRNA-7. Also, a treatment could be devised for the opposite case – for people with a predisposition to a pathologically low body weight.