Disabling Genes in Immune Cells Prevents Obesity

Obesity is a $1.7 trillion problem in the United States, a condition that leads to several chronic illnesses including heart disease, stroke and certain types of cancer. For many, this results in preventable, premature death. Unsurprisingly, identifying clinical strategies to prevent obesity from a pharmacological, or even a genetic standpoint have been in the research spotlight for decades.

Scientists at the Washington University School of Medicine are exploring the possibility of targeting obesity on a genetic level. By switching off a specific gene in immune cells of mice, they successfully stopped mice fed a high-fat diet from becoming obese. The study was published in The Journal of Clinical Investigation.

Obesity and inflammation are intricately linked. The number of macrophages in adipose, or fat tissue, differs depending on an individual’s metabolic status. Lean humans have around 10 percent of macrophages in adipose tissues, while obese people have up to 40 percent. Experts believe that this increased number and activity of macrophages could be linked to metabolic perturbations and the onset of associated chronic diseases in obese individuals.

By disabling the ASXL2 gene in macrophages, the researchers hypothesized that this would curb chronic low-grade inflammation in fat tissues and in turn, help resist excess weight gain in spite of high-fat diets. Their experimental model involved either genetically modifying macrophages in obese mice, or injecting them with nanoparticles that specifically target and shut off ASXL2.

Interestingly, despite being fed a high calorie diet, the treated mice burnt 45 percent more calories than mice with active macrophage ASXL2.

Principal investigator of the study, Steven L. Teitelbaum, MD, 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.”

Sources: The Journal of Clinical Investigation, Washington University in St. Louis.