IRX3 Made Me This Way

A holy grail of obesity research is to find the genes and their products behind it. For a while it looked like mutations in a gene called FTO was responsible. But a new study reveals the FTO mutation is actually affecting another gene that does make someone more apt to be obese.

It's called IRX3 and is quite a distance from the FTO gene. What's also interesting is how the two interact. Genes have an area that control gene expression and segments that don't code called introns. Researchers saw that the mutated FTO intron wasn't affecting the FTO gene expression. Rather, it enhanced the expression of the distant IRX3 gene.

To test their theory that the IRX3 gene is an obesity gene, researchers engineered mice without it. These mice turned out to be much leaner than normal mice, even though they ate the same foods and were equally active. When they were fed a high fat diet, they remained lean while the normal mice doubled in weight. These mice had smaller fat cells and more brown fat which is healthier.

We humans also carry brown fat which generates body heat while the less healthy white or yellow fat is stored on our waist and thighs. The mice with no IRX3 were also better able to process glucose making them more resistant to diabetes. These results were confirmed in humans when researchers studied brain samples from 153 people of European ancestry.

Their FTO mutations also were associated with IRX3 expression and affected their obesity risk. Scientists plan to study exactly how IRX3 gene expression affects other genes in order to develop new drugs that could one day be used to treat obesity.