Enzyme allows mice to eat more, and gain less weight

Mice altered to express the IKKbeta enzyme (right column) in their fat had smaller globules of fat in their subcutaneous adipose tissue (top row) and in their liver (bottom row) than normal mice (left column). (Credit: Xu Lab)

Scientists have genetically engineered mice able to express a certain enzyme, which allows for an increased metabolic rate. The lab mice infussed with this enzyme in their fat tissue were able to eat more, but gain far less weight than their naturally bred brethren.

It’s generally acknowledged that obesity and inflammation cause insulin resistance, however it’s not perfectly understood why this happens. Embarking on a research that seeks to clarify how obesity and inflammation affect insulin resistance, Brown University researchers changed the sequence of events for transgenically engineered mice by inducing inflammation via the IKKbeta enzyme in their fatty tissue before they were obese.

They then procedeed in administrating a fatty diet to two groups of mice, one altered, the other natural, with all mice starting at the same weight. They observed that 22 weeks on a high-fat diet, however, altered male mice weighed less than 38 grams while unaltered male mice weighed more than 45 grams. After switching to a less fatty diet, the weight differences between the two groups weren’t as evident, however they remained statistically significant.

“Turning on this molecule has a very dramatic impact on lipid metabolism,” says Haiyan Xu, assistant professor of medicine at Brown University and corresponding author of a paper describing the research published online in the journal Endocrinology.

The altered mice not only managed to eat more and gain less weight, but due to their accelerated metabolism, researchers could observe they had lower sugar levels in their blood, after a glucose shot, than those of the control mice. An insulin shot was also administered, and researchers also remarkably observed how insulin was more effective.

Scientists are now trying to figure out the mechanisms through which IKKbeta enzyme can increase metabolic performance. One thing’s for certain for the researchers responsible for the study: obesity and inflammation are both promoters of insulin resistance, and obesity seems to be the worse one, Xu says. “Lower body weight is always a beneficial thing for influencing insulin sensitivity. Reduced adiposity wins over increased inflammation.”


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