Gene Disabling Nanoparticles Prevent Obesity In Animal Studies

The activity of immune cell macrophages' ASXL2 gene was blocked because they are key inflammatory cells and obesity is associated with chronic low grade inflammation, it is believed that reducing inflammation may help to regulate weight gain and obesity according to the researchers. 

“We've developed a proof of concept here that you can regulate weight gain by modulating the activity of these inflammatory cells," said principal investigator Steven L. Teitelbaum, MD, the Wilma and Roswell Messing Professor of Pathology & Immunology. "It might work in a number of ways, but we believe it may be possible to control obesity and the complications of obesity by better regulating inflammation."

When obese less calories are burnt than by those who are not obese, and the same is true for mice. Obese mice were found to maintain the same levels of calories burning as the mice that were not obese after the gene ASXL2 was deleted in the macrophages of the obese mice, according to co-first author Wei Zou, MD, Ph.D., and in a second set of experiments after they injected nanoparticles that interfere with the gene’s activity in the animals. 

Despite being fed high fat diets the treated mice burned 45% more calories than their obese untreated counterparts with functioning ASXL2 genes in their macrophages. While it is not exactly clear why this prevented obesity in the mice it appears to involve getting white fat cells to behave more like brown fat cells says co-author Nidhi Rohtagi. 

While this strategy is a long way from being understood and ready to become a therapy, it has the potential to help obese people to burn fat at rates that are similar to those seen in leaner people. 

"A large percentage of Americans now have fatty livers, and one reason is that their fat depots cannot take up the fat they eat, so it has to go someplace else," Teitelbaum said. "These mice consumed high-fat diets, but they didn't get fatty livers. They don't get type 2 diabetes. It seems that limiting the inflammatory effects of their macrophages allows them to burn more fat, which keeps them leaner and healthier."