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According to a new study in mice, a history of obesity caused by a high-fat diet leads to changes in innate immunity that promote inflammatory diseases — changes that persist
even after weight loss and a return to normal metabolism.
If the findings apply to humans as well, the authors suggest that these epigenetic changes may contribute to susceptibility to age-related neuroinflammatory diseases associated with obesity
.
Age-related macular degeneration is a neuroinflammatory disease that is the leading cause of irreversible blindness in older adults and is associated with
obesity.
However, the mechanism by which obesity causes people to develop this disease is not well defined
.
Perhaps relatedly, the long-term effects of previous obesity on later immune responses are also still unknown
.
In a series of mouse experiments, Masayuki Hata and his colleagues found that adipose tissue macrophages in mice fed a high-fat diet showed epigenetic changes that led to increased
expression of genes that play a role in the inflammatory response.
The authors said this expression continued after the mice regained normal weight and returned to normal metabolism
.
According to Hata et al.
, these persistent epigenetic changes occur during obesity, when fatty acids like stearic acid alter the pro-inflammatory phenotype of fat macrophages, which is preserved during aging
.
These resident inflammatory cells can transfer to other parts of the body, including the eyes, where they initiate inflammatory procedures that promote age-related macular degeneration
.
"The study by Hata et al.
raises important questions about the upstream pathways responsible for epigenetic reprogramming in macrophages and whether targeting these pathways can reverse epigenetic changes," Kevin Mangum and Katherine Gallagher wrote
in Related Thoughts.