Scientists Find Inflammation 'Switch' in Obesity

Scientists just solved a mystery that's puzzled doctors for decades: why does obesity turn on the body's inflammation alarm and leave it running?

A team at UT Southwestern Medical Center found the molecular "switch" responsible. Their discovery, published in Science, could help nearly 900 million adults worldwide living with obesity avoid type 2 diabetes, heart disease, and other inflammation-related conditions.

"It's been known for a long time that obesity causes uncontrolled inflammation, but no one knew the mechanism behind it," said Dr. Zhenyu Zhong, Assistant Professor of Immunology at UT Southwestern. "Our study provides novel insights about why this inflammation occurs and how we might be able to stop it."

The researchers compared immune cells from lean and obese people, plus mice on different diets. In both obese humans and mice fed high-fat diets, they spotted something unusual: a protein complex called NLRP3 was working overtime, pumping out inflammatory signals.

Digging deeper, the team found damaged DNA piling up inside cellular power plants called mitochondria. An enzyme that normally cleans up DNA building blocks had been switched off through a process called phosphorylation.

Without this cleanup crew working properly, DNA fragments accumulated and triggered the inflammation alarm. The researchers proved this by removing the enzyme gene in mice and even zebrafish. These animals developed the same inflammation problems, with many mice developing diabetes and fatty liver disease.

The Ripple Effect shows just how far this discovery could reach. The team identified three potential ways to interrupt the inflammation cascade: reactivate the cleanup enzyme, block DNA fragments from reaching mitochondria, or prevent damaged DNA from triggering the alarm system.

Each approach could become a new therapy for millions of people. Rather than just treating the symptoms of obesity-related diseases, doctors might soon target the root cause of inflammation itself.

Dr. Zhong's team is now investigating why obesity switches off the cleanup enzyme in the first place. Understanding that step could unlock even more treatment options.

This breakthrough transforms obesity from an unsolvable inflammation puzzle into a problem with specific molecular targets that scientists can work on fixing.