A history of obesity caused by a high-fat diet produces changes in innate immunity that can promote inflammatory disease – changes that persist even after weight loss and a return to normal metabolism, according to a new study in mice. If such findings translate to humans, the authors suggest that these epigenetic changes could contribute to predisposition to age-related neuroinflammatory diseases associated with obesity.

Age-related macular degeneration, a neuroinflammatory disease and major cause of irreversible blindness in older people, has been linked to obesity. However, the mechanisms through which obesity predisposes one to the condition aren’t well defined. Perhaps related, the long-term impact of prior obesity on the immune response later in life also remains unknown.

Across a series of experiments in mice, the researchers show that adipose tissue macrophages from mice fed a high-fat diet exhibit epigenetic changes that led to increased expression of genes that function in inflammatory responses. This expression continued after mice returned to a normal weight and regained metabolic normalcy, the authors say.

According to the authors these persistent epigenetic changes occurred during an obese period when fatty acids like steric acid altered adipose resident macrophages toward a proinflammatory phenotype, which is retained during aging. These resident inflammatory cells can travel to other parts of the body, including the eye, where they initiate an inflammatory program that promotes age-related macular degeneration.

https://www.science.org/doi/10.1126/science.abj8894