A new study in mice demonstrates a history of obesity caused by a high-fat diet produces changes in innate immunity that can promote inflammatory disease. If the findings translate to humans, the authors suggest that these epigenetic changes could contribute to predisposition to age-related neuroinflammatory diseases associated with obesity.

The findings, “Past history of obesity triggers persistent epigenetic changes in innate immunity and neuroinflammation,” is published in Science.

Age-related macular degeneration has been linked to obesity. Yet, the mechanisms through which obesity predisposes one to the condition aren’t fully understood.

“Age-related macular degeneration is a prevalent neuroinflammatory condition and a major cause of blindness driven by genetic and environmental factors such as obesity,” wrote the researchers. “In diseases of aging, modifiable factors can be compounded over the life span. We report that diet-induced obesity earlier in life triggers persistent reprogramming of the innate immune system, lasting long after normalization of metabolic abnormalities.”

Masayuki Hata, PhD, senior lecturer and chief of macular clinic at Kyoto University, and colleagues showed that adipose tissue macrophages from mice fed a high-fat diet, exhibited 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 said. The researchers observed 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.

“The study by Hata et al. raises important questions about the upstream pathways that are responsible for epigenetic reprogramming in macrophages and whether targeting these pathways can reverse epigenetic changes,” wrote Kevin Mangum, MD, PhD, and Katherine Gallagher, MD, both at the University of Michigan, in a related Perspective.

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