Scientists have known for quite a while that obesity increases the chances of colon cancer, but hey were unable to figure out why. Now, they might have the answer.

Lab mouse. Photo by Rama.

Obese mice, just like obese humans, are at an increased risk of colon cancer. Researchers found that overweight mice showed an increasein intestinal stem cells due to activation of a protein called PPAR-δ that regulates metabolism. If the same stands for humans, this could help explain a medical mystery:

“For quite some time there’s been an understanding that obesity leads to an increase in cancer in many tissues,” says Ömer Yilmaz, a cancer biologist at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT) in Cambridge, and one of the leaders of the study. “We really wanted to understand the mechanism behind this.”

Yilmaz teamed up with David Sabatini, who studies metabolism at MIT to find out more about the connection between cancer and obesity. They fed mice a high-fat, high-calorie diet for a year and then tested the effects of the diet on the number and function of stem cells in their intestines.

They found that the 60% fat diet not only made mice become overweight, but also activated PPAR-δ and stimulated the proliferation of intestinal stem cells. This rise in stem cells was consistently associated with a rise in tumors.

However, what isn’t clear is if this rise in tumors is caused by the mice becoming overweight or by the fatty foods directly. Also, while the relationship seems very similar to what has been reported in humans, this may not necessarily be the case. We could be dealing with “a mechanism in search of a relation that doesn’t exist in humans”, cautions Walter Willett, who studies nutrition at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. Yilmaz also remarks that epidemiological studies like this one can be muddled by confounding variables.

”The data linking fat intake to cancer incidence is a mixed bag,” he says.

He and his team now want to isolate individual factors and pinpoint the decisive factor that links obesity to colon cancer.

Nature doi:10.1038/nature.2016.19484