Disabling Immune Cell Genes: A New Frontier in Obesity Prevention
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Understanding the Link Between Obesity and Inflammation
Obesity presents a staggering $1.7 trillion challenge in the United States, contributing to various chronic health conditions like heart disease, stroke, and certain cancers. This alarming trend frequently leads to preventable early mortality. As a result, the scientific community has focused on developing clinical interventions, both pharmacological and genetic, to combat obesity for many years.
Recent research from Washington University School of Medicine has opened a new avenue in addressing obesity at the genetic level. By turning off a specific gene in the immune cells of mice, the researchers effectively prevented these mice, who were fed a high-fat diet, from gaining weight. The findings were published in The Journal of Clinical Investigation.
The Role of Macrophages in Fat Tissue
Obesity is closely associated with inflammation. The quantity of macrophages in adipose (fat) tissue varies with an individual’s metabolic state. Lean individuals typically harbor about 10 percent macrophages in their adipose tissues, whereas this figure can rise to 40 percent in obese individuals. Researchers speculate that the heightened presence and activity of macrophages may contribute to metabolic disruptions and the emergence of chronic diseases in those with obesity.
By disabling the ASXL2 gene in macrophages, the researchers believed they could reduce chronic low-grade inflammation in fat tissues, which might help in resisting weight gain despite high-fat diets. Their experimental design included either genetically altering macrophages in obese mice or administering nanoparticles that specifically inhibit ASXL2.
Surprisingly, the treated mice burned 45 percent more calories than those with active macrophage ASXL2, even while consuming a high-calorie diet.
Insights from the Research
Principal investigator Steven L. Teitelbaum, MD, remarked, “These mice were on high-fat diets, yet they didn’t develop fatty livers or type 2 diabetes. It appears that minimizing the inflammatory response of their macrophages enables them to metabolize fat more effectively, helping them maintain a healthier weight.”
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Sources: The Journal of Clinical Investigation, Washington University in St. Louis.