Researchers say they have finally discovered the pathway by which obesity causes runaway inflammation that can lead to a host of health issues such as diabetes and liver disease.

“It’s been known for a long time that obesity causes uncontrolled inflammation, but no one knew the mechanism behind it. Our study provides novel insights about why this inflammation occurs and how we might be able to stop it,” study leader Zhenyu Zhong of UT Southwestern said in a statement.

It was already known ‍that inflammation in the absence of an infection is largely driven by a sensor protein complex in immune cells known as NLRP3, which ‍converts immature inflammatory molecules to mature ones that stimulate inflammation.

When the researchers compared immune cells from lean and obese human volunteers and from mice fed regular and high-fat diets, they found excessive NLRP3 activity in the obese people and the high-fat-consuming rodents, according ⁠to a report published in Science.

The immune cells with excessive NLRP3 activity had large amounts of damaged DNA in their mitochondria, the cells’ energy factories, which the researchers attributed to excessive amounts of DNA building blocks called nucleotides.

The reason for the extra nucleotides is that an enzyme called SAMHD1, which ​ordinarily degrades the nucleotides, had been turned off, the researchers also discovered.

When they turned off the same enzyme in mice by deleting the gene for it, they created the same inflammatory phenomenon. They saw excess nucleotides in the immune cells, large amounts of damaged DNA in the cells’ energy factories, overactive NLRP3 protein complexes, and eventually, inflammation-related type 2 diabetes and fatty liver disease.

The ‍new findings suggest inflammation in obesity occurs through a molecular cascade kicked off by inactivation of SAMHD1, Zhong said.

The discovery suggests multiple potential approaches researchers could explore to ⁠prevent such inflammation.

They could look at ways to stop the inactivation of SAMHD1, so that DNA building blocks would not accumulate, for example. Another might be to somehow block the delivery of the extra DNA building blocks to the mitochondria.

A third approach might be to block the damaged mitochondrial DNA from attaching to NLRP3, preventing immune cell maturation.