Deleting immune cell genes prevents obesity in mice on high-fat diet

Being able to eat whatever we want and still stay slim is many people’s dream come true. And while it still remains firmly in fantasy territory for now, new research may have brought it a step closer to reality. By blocking a gene in certain immune cells, scientists have prevented mice from becoming obese, even on a high-fat diet.

The immune cells at the center of the study are known as macrophages. These cells are responsible for inflammation responses, which are crucial for destroying pathogens. Chronic low-grade inflammation is also known to occur in people with obesity.

For the new study, researchers from Washington University School of Medicine in St. Louis investigated whether reducing that inflammation could help cut down on weight gain. To do so, the team blocked a gene called ASXL2 in the macrophages.

In one group of mice, the researchers deleted the ASXL2 gene from the animals’ macrophages. In a second group, the mice were instead injected with nanoparticles that disrupt the gene’s activity. Both groups were fed high-fat diets for six weeks, as was a control group that received no treatment and had a fully functioning ASXL2 gene.

The team found that the treated mice managed to keep the pounds off, burning 45 percent more calories than the untreated group. Strangely enough, the researchers aren’t entirely sure why the treatment works, but it appears to involve making white fat act more like brown fat. White fat is the stuff that stores energy, while brown fat burns it.

Importantly, the mice also avoided the run-on health effects that come with obesity. If the treatment is ever able to be adapted to humans, it could help relieve a huge burden on healthcare systems.

“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,” says Steven Teitelbaum, principal investigator on the study. “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.”

Of course, for now the treatment is limited to mice, and there’s a good chance that it will never make it to humans. For now at least, healthy eating and exercise remain the most effective ways to stave off obesity.

The research was published in The Journal of Clinical Investigation.

Source: Washington University School of Medicine in St. Louis

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