Obesity Triggers Pathogenic Epigenetic Changes That Persist After Weight Loss

Diet-induced obesity earlier in life can lead to lasting changes in the innate immune system that promote neuroinflammatory disease, even after weight loss and a return to normal metabolism, according to a new study appearing in this week's Science. In diseases of aging, modifiable factors such as obesity can be compounded over the lifespan, and prior studies have shown that weight loss in obese individuals can reduce obesity-associated inflammation and restore glycemic control. The long-term impact of prior obesity, however, is poorly understood. In the new study, scientists from the University of Montreal and collaborators focused on age-related macular degeneration (AMD), a neuroinflammatory disease of the aging eye that is caused by genetic and other risk factors including obesity. In experiments involving mice that had been fed a high-fat diet to induce obesity then switched to a regular healthy diet, the researchers find that adipose tissue macrophages from the animals exhibited epigenetic changes that led to increased expression of genes that function in inflammatory responses and, importantly, that this expression continued even after the mice regained normal metabolic functioning with a shift to a normal diet. The epigenetic changes, according to the study's authors, occurred when the mice became obese and fatty acids like steric acid altered adipose resident macrophages toward a persistent proinflammatory phenotype. The macrophages can migrate to other parts of the body including the eye, where they promote AMD