Title: Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation
Author: Masayuki Hata, Elisabeth M. M. A. Andriessen, Maki Hata, Roberto Diaz-Marin, Frédérik Fournier, Sergio Crespo-Garcia, Guillaume Blot, Rachel Juneau, Frédérique Pilon, Agnieszka Dejda, Vera Guber, Emilie Heckel, Caroline Daneault, Virginie Calderon, Christine Des Rosiers, Heather J. Melichar, Thomas Langmann, Jean-Sebastien Joyal, Ariel M. Wilson, Przemyslaw Sapieha
Issue&Volume: 2023-01-06
Abstract: Age-related macular degeneration is a prevalent neuroinflammatory condition and a major cause of blindness driven by genetic and environmental factors such as obesity. 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. Stearic acid, acting through Toll-like receptor 4 (TLR4), is sufficient to remodel chromatin landscapes and selectively enhance accessibility at binding sites for activator protein-1 (AP-1). Myeloid cells show less oxidative phosphorylation and shift to glycolysis, ultimately leading to proinflammatory cytokine transcription, aggravation of pathological retinal angiogenesis, and neuronal degeneration associated with loss of visual function. Thus, a past history of obesity reprograms mononuclear phagocytes and predisposes to neuroinflammation.
DOI: abj8894
Source: https://www.science.org/doi/10.1126/science.abj8894