Obesity prevented in mice treated with gene-disabling nanoparticles

By disabling a gene in mouse-specific cells, researchers at the University of Washington School of Medicine in St. Louis have prevented the mice from becoming obese, even after the animals have been fed a high-fat diet .

The researchers blocked the activity of a gene in immune cells. Because these immune cells, called macrophages, are key inflammatory cells, and because obesity is associated with chronic low-grade inflammation, the researchers believe that reducing inflammation can help regulate weight gain and obesity.

The study is published May 1 in The Journal of Clinical Research.

“We have developed a proof of concept here that can regulate weight gain by modulating the activity of these inflammatory cells,” said lead investigator Steven L. Teitelbaum, MD, professor of pathology and immunology at Wilma and Roswell Messing. “It can work in several ways, but we believe that it is possible to control obesity and the complications of obesity through better regulation of inflammation.”

When people are obese, they burn fewer calories than those who are not obese. The same is true for mice. But according to co-author Wei Zou, MD, Ph.D., an assistant professor of pathology and immunology, the researchers found that obese mice maintained the same level of calorie burning as non-obese mice, after the The research team removed the ASXL2 gene from macrophages in obese mice and, in a second set of experiments, after injecting animals with nanoparticles that interfere with the gene’s activity.

Despite high-fat diets, treated animals burned 45% more calories than their obese bedmates with a functional gene in macrophages.

It is unclear exactly why this prevented obesity in the mice. Co-author Nidhi Rohatgi, a pathology instructor, said it appears to imply that white fat cells, which store fat that makes us obese, behave more like brown fat cells, which help burn stored fat. The strategy is a long way from becoming a therapy, but it has the potential to help obese people burn fat at rates similar to those seen in lean people.

“A large percentage of Americans now have fatty livers, and one reason is that their fat stores cannot absorb the fat they eat, so they have to go somewhere else,” Teitelbaum said. “These mice ate high-fat diets, but didn’t get fatty livers. They don’t have type 2 diabetes. It seems that limiting the inflammatory effects of their macrophages allows them to burn more fat, keeping them slimmer and healthier.”