A history of obesity alters innate immunity and neuroinflammation.

According to a recent study in mice, a history of obesity brought on by a high-fat diet results in innate immune modifications that can promote inflammatory disease. These changes endure even after weight loss and a return to normal metabolism. The scientists speculate that these epigenetic modifications may increase the risk of developing age-related neuroinflammatory illnesses linked to obesity if such findings apply to humans.

Obesity has been associated with age-related macular degeneration, a neuroinflammatory condition that is a leading cause of permanent blindness in older adults. The mechanisms by which obesity predisposes one to the illness, however, are not clearly understood. The long-term effects of past obesity on the immune response later in life are also unknown, which may be connected. Masayuki Hata and colleagues demonstrate through a series of mouse tests that animals fed a high-fat diet have epigenetic modifications that result in enhanced expression of genes involved in inflammatory responses in their adipose tissue macrophages. The scientists report that this expression persisted even after the mice's metabolism and weight stabilized.

According to Hata et al., proinflammatory phenotypes in adipose resident macrophages were altered by fatty acids such as steric acid during an obese stage and are maintained throughout aging. These localized inflammatory cells can move to several bodily regions, including the eye, where they start an inflammatory process that encourages age-related macular degeneration. In a related Perspective, Kevin Mangum and Katherine Gallagher state that "the discovery by Hata et al. raises fundamental concerns concerning the upstream mechanisms that are accountable for epigenetic reprogramming in macrophages and whether targeting these pathways can correct epigenetic alterations."