Macrophages are found in various organs throughout the body, including fat tissue. Recent research suggests that fat-tissue macrophages control systemic metabolism by influencing norepinephrine signaling in the fat itself, but how those macrophages exert that influence is not fully understood.

In a study published online on January 3, 2023 in Nature Communications, Nicholas Sibinga, M.D., and colleagues have identified a key role for the protein AIF1 (allograft inflammatory factor-1). AIF1 induces macrophages to express the enzyme MAOA, which in turn degrades norepinephrine. The researchers found that male mice lacking the gene for AIF1 had elevated levels of norepinephrine in their fat tissue; when those mice were fed a high-fat diet, they were protected against obesity, glucose intolerance, and insulin resistance. These initial findings, plus examination of human fat samples, suggest possible connections between the AIF1 gene and human obesity.

Dr. Sibinga is professor of medicine and developmental & molecular biology at Einstein.