Study Identifies Low microRNA-7 as Obesity Risk Factor

Researchers in Switzerland have determined that an endogenous microRNA molecule known as microRNA-​7 is a non-classic genetic risk factor for hereditary obesity.

Heredity plays a role in how strongly we are predisposed to put on excess weight. In recent years, researchers have identified roughly one hundred genes that influence an individual’s susceptibility to obesity. 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 are the result of factors like epigenetics, which although part of our DNA, are not genes in the classical sense. 

Like genes, the blueprints for microRNA molecules are part of our chromosomes. But while genes act as the building instructions for proteins, the information contained in microRNA is not translated into protein form. Instead, the microRNA molecules act in our cells in the form of RNA.

“MicroRNA-​7 is the first microRNA for which we’ve been able to demonstrate an association with obesity,” says Markus Stoffel, Professor at ETH Zurich’s Department of Biology.  

Stoffel and colleagues bred mice in which microRNA-​7 was missing in certain nerve cells of the hypothalamus, the control center between the endocrine system and nervous system. These mice demonstrated a pathologically increased appetite and became obese.

The ETH researchers were also able to demonstrate such a link in humans. Together with scientists from the University of Cambridge, they analyzed genomic and medical data, including the anonymized data held in a British database relating to 500,000 people. This allowed Stoffel and his colleagues to show that people with genetic variations on their chromosomes near the blueprint for microRNA-​7 are heavier and bigger than average. The consequence of these genetic variations is that the above-​mentioned nerve cells of the people affected produce less microRNA-​7.

The authors of the study—published recently in Nature Communications—were also able to show that microRNA-​7 in these cells affects a biochemical pathway known to be instrumental in maintaining the body’s energy balance, regulating appetite and controlling the production of growth hormones. MicroRNA acts there by regulating the production of proteins.

“Up to now, it was unclear why genetic variations were only able to provide an explanation for less than half the causes of hereditary obesity,” Stoffel says. “Our study now shows that it’s not enough to look for the answer solely in the genes that encode information for proteins. The parts of DNA outside the genes also have to be examined, such as the regions containing the blueprints for microRNA.”

The findings could lead to a treatment for people who are obese because their hypothalamus producing insufficient amounts of microRNA-​7. microRNA-​7 could also be pharmacologically inhibited to treat those with a predisposition to pathological low body weight.