Enzyme Significantly Reduces Weight Gain in Mice

Enzyme Significantly Reduces Weight Gain in MiceA new study found that an enzyme called IKKbeta was linked to increased metabolism in lab mice. When researchers engineered the mice to express the IKKbeta enzyme in their fat tissue, the mice ate more food yet gained less weight, with their bodies using fat and sugar more effectively than mice who had not been treated. The study was published in the online edition of the journal “Endocrinology.”

The researchers working on the study reported that the expression of the enzyme had several positive benefits, including improving the efficacy of insulin, reducing weight gain, and improving metabolism. The mice were also less likely to become obese, though in exchange they experienced significant inflammation. Still, the researchers say that the findings could lead to new discoveries regarding the effect that inflammation and obesity have on insulin sensitivity and insulin resistance.

“Turning on this molecule has a very dramatic impact on lipid metabolism,” says Haiyan Xu, an assistant professor of medicine at the Warren Alpert Medical School of Brown University and a researcher at the Center for Diabetes and Endocrinology of Rhode Island Hospital.

In this study, scientists sought to explore the effects of obesity and inflammation on insulin resistance. Both obesity and inflammation appear to cause insulin resistance, but obesity plays a larger role, and the most popular hypothesis among scientists is that obesity causes inflammation, which contributes to insulin resistance. By expressing the IKKbeta hormone in the fatty tissue of lab mice, the researchers reduced inflammation before they mice were obese; the mice then showed increased metabolism, significantly higher than control mice that did not have the enzyme expressed.

The mice who expressed the enzyme still put on weight, but at a significantly reduced rate. When the mice were fed high-fat diets, altered mice weighed less than 38 gram; control mice weighed over 45 grams. The difference was less pronounced when the mice were fed a healthier diet—called “chow”—but it was still statistically significant. Both male and female mice showed improved metabolism and less weight gain when the enzyme was expressed.

The altered mice actually ate more food, but gained weight more slowly, which demonstrated to the researchers that their metabolic rates were increased over the control mice. Altered mice also displayed lower blood sugar levels after being injected with glucose, and they maintained their lower blood sugar levels after an injection with insulin, which suggests that insulin was more effective for them as well. The altered mice expended more energy than the control mice, which suggests that they successfully metabolized the glucose injections.

The researchers stated that they were not sure about the mechanism by which IKKbeta improves metabolic performance. However, according to Xu, it appears that obesity is a greater factor in causing insulin resistance than inflammation.

“Lower body weight is always a beneficial thing for influencing insulin sensitivity,” said Xu. “Reduced adiposity wins over increased inflammation.”

Previous research has explored the effects of IKKbeta by activating it in the liver, where it seemed to have no effect on weight gain, and in the hypothalamus, where it actually increased weight gain. The findings of the study suggest that IKKbeta’s improvements to metabolic processes are dependent on its expression within fatty tissue.

The study was funded by Brown University as well as the American Heart Association, with a scientist development grant to Xu.