Eating too much food activates a typically dormant immune system pathway in the brain. This process sends out immune cells to attack and destroy invaders that are not there, according to Dongsheng Cai of the University of Wisconsin-Madison.
The findings were published in the journal Cell. The research could help explain why obesity causes so many different diseases.
"This pathway is usually present but inactive in the brain," Cai said.
Obesity is a growing problem worldwide with 1.8 billion people estimated to be overweight or obese in 2007.
Cai's team studied mice, and tried to explain previous studies that have shown that obesity causes chronic inflammation throughout the body.
Inflammation is found in a range of diseases related to obesity, including heart disease and diabetes.
Researchers focused on a compound known as IKKbeta/NK-kappaB.
Cai's team found the compound in the hypothalamus, a part of the brain linked with both metabolism in mice and humans.
They wrote, "The hypothalamus is the 'headquarters' for regulating energy.”
When researchers fed mice a high-fat diet, it became extremely active.
The body ignored signals from leptin when the body was active. Leptin is a hormone that normally helps regulate appetite, and insulin, which helps convert food into energy.
Stimulating IKKbeta/NK-kappaB made the mice eat more, while suppressing it made them eat less.
Cai said the research points a master switch for the diseases caused by overeating.
"Hypothalamic IKKb/NF-kB could underlie the entire family of modern diseases induced by overnutrition and obesity," his team said.
Cai does not know why this compound is in the brain and in the immune system.
Scientists hypothesize it evolved long ago in primitive animals that do not have the same sophisticated immune system as modern animals, including mice and humans.
"Presumably it played some role to guide the immune defense," Cai said. "In today's society, this pathway is mobilized by a different environmental challenge – over nutrition."
"Knocking out" the gene using genetic engineering kept mice eating normally and prevented obesity.
Cai say this cannot be done in people but instead believes a drug, or even gene therapy, might work.
Gene therapy means a virus is used to carry corrective DNA into the body, but the approach is still highly experimental.