Some Mice Pig Out But Don't Get Fat

Mice lacking a certain gene can eat junk food without getting fat, a new study finds.

Researchers can't say yet if the same gene affects human weight gain, and they say more research is needed to investigate that possibility.

The gene is called IKKe, and it prompts the production of enzymes called kinases.

Mice without the gene are also less likely to experience chronic inflammation or fatty liver and insulin resistance when on a lousy diet, the study found.

"Perhaps most interestingly, the mice burn more calories even though they aren't eating any less or exercising more," said Alan Saltiel of the University of Michigan, Ann Arbor. They apparently keep the weight off on a diet loaded with fat by "producing a little heat."

The findings are detailed in the Sept. 4 issue of the journal Cell.

Growing evidence has linked the insulin resistance in obesity to a state of chronic, low-grade inflammation. Saltiel's group suspected that IKKe had a role in eliciting that inflammatory state.

Earlier studies have found that if you stop the inflammatory chain of events in obesity, you can break the link between obesity and diabetes, Saltiel said. In the current study, "we expected to disrupt that link, but instead we stopped the onset of obesity," he said.

Further analysis of gene activity within mice lacking IKKe offered more clues to its influence. Loss of the gene reduces the expression of inflammatory cytokines, along with certain regulatory proteins and enzymes involved in glucose and lipid metabolism.

The researchers suspect that IKKe's effects involve the interplay between the liver, fat and immune response in obesity. It may not play a role in the initial inflammatory response to a high-fat diet, but might be required for sustaining that state, they say.

Additional research could show whether IKKe might be a good target for drugs aimed at making humans healthy, the researchers say.