Figure 1.

Potential roles of neutrophil-derived MPO in insulin resistance and obesity. In this issue, Wang and colleagues (10) demonstrate that when mice consume a high-fat diet rich in calories, neutrophils infiltrate white and brown adipose tissue. Following activation by unknown mechanisms, the neutrophils release MPO, which uses hydrogen peroxide to generate a wide array of oxidizing intermediates. Oxidative damage of specific targets promotes insulin resistance and impairs thermogenesis, resulting in decreased energy expenditure, elevated glucose concentrations, further weight gain, and diabetes. Mice deficient in MPO are protected from diet-induced obesity and insulin resistance, raising the possibility that selective inhibitors of MPO might be able to prevent or treat insulin resistance in obese humans.