PROVIDENCE, R.I. [Brown University] In a new study, scientists report that they substantially curbed weight gain, improved metabolism, and improved the efficacy of insulin in mice by engineering them to express a specific human enzyme in their fat tissue. Although the obesity prevention came at the significant cost of widespread inflammation, the research offers new clues about the connections among obesity, insulin resistance and type 2 diabetes, and inflammation.
"Turning on this molecule has a very dramatic impact on lipid metabolism," said Haiyan Xu, assistant professor of medicine (research) in the Warren Alpert Medical School of Brown University and a researcher at Rhode Island Hospital's Hallett Center for Diabetes and Endocrinology. Xu is the corresponding author of a paper describing the research in the January 2012 issue of Endocrinology and released early online.
The relationship between fat, inflammation, and insulin performance is complex. The conventional wisdom is that obesity leads to inflammation which contributes to insulin resistance. In this study, the researchers changed the sequence of events for transgenically engineered mice by inducing inflammation via the enzyme IKKbeta in their fatty tissue before they were obese. The result for metabolism was much more positive than for control mice who were left unaltered but were fed the same diets.
For both male and female mice, the ones who were altered still put on weight but significantly more slowly. All the mice started at the same weight. After about 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. On a less extravagant diet named "chow" the difference was considerably lessened but was still statistically significant. Both trends held for females as well.
The altered mice experienced slower weight gain despite eating much more food. Their increased metabolism al
|Contact: David Orenstein|