Dr. Masayuki Hata, Université de Montréal
Scientific publication
Hata M, Andriessen EMMA, Hata M, Diaz-Marin R, Fournier F, Crespo-Garcia S, Blot G, Juneau R, Pilon F, Dejda A, Guber V, Heckel E, Daneault C, Calderon V, Des Rosiers C, Melichar HJ, Langmann T, Joyal JS, Wilson AM, Sapieha P. Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation. Science. 2023 Jan 6;379(6627):45-62. doi: 10.1126/science.abj8894. Epub 2023 Jan 5. PMID: 36603072.
A history of obesity triggers changes in immunity that could contribute to age-related macular degeneration
Research by post-doctoral fellow Masayuki Hata has identified a new molecular mechanism linking obesity to age-related macular degeneration (AMD), a major cause of irreversible blindness that affects around 196 million people worldwide. While genetic predisposition increases the risk of AMD, it is not the definitive cause, which underlines the role of environmental and lifestyle factors. This research has shown that stress factors such as obesity can reprogram innate immune cells, causing them to behave destructively towards aging eyes even after obesity is improved. Using obesity as a stressor model, the researchers found that past history of obesity induces long-lasting chromatin architectural changes in innate immune cells, prompting them to produce inflammatory molecules. These findings shed light on the biology of the immune cells responsible for AMD and pave the way for future targeted therapies. The implications of this study could also extend to other diseases linked to neuroinflammation, such as Alzheimer’s disease and multiple sclerosis.
While past history of obesity has been associated with increased risk of many age-related diseases, the mechanism by which this occurs was unknown. In a mouse model Masayuki Hata and colleagues found that in obesity free fatty acids alter immune cells called adipose tissue macrophages to make them pro-inflammatory. These modified cells can then travel to the eye, where their inflammatory effect promote AMD. Therapeutic avenues that reprogram macrophages or eliminate subpopulations of pro-inflammatory cells could delay the onset of AMD.
The better understanding of the mechanisms linking obesity and AMD is expected to lead to preventive medical treatment that could greatly reduce the burden of disease of aging for patients and society. The researchers further hope their discovery will lead other scientists to broaden their interest beyond obesity-related diseases to other diseases characterized by increased neuroinflammation, including Alzheimer’s disease and multiple sclerosis. It could extend healthy life expectancy by preventing frailty, thus making a significant social contribution.
About Dr. Masayuki Hata
Dr. Masayuki Hata performed this research as a post-doctoral fellow in the laboratory of Dr. Przemyslaw (Mike) Sapieha at the Maisonneuve-Rosemont Hospital Research Centre, affiliated to University of Montreal. As first author of this study, he designed & performed the research, analyzed the data, and wrote the paper with contributions from other co-authors.
Dr. Masayuki Hata is currently Asssociate Professor in the Department of Ophthalmology and Visual Sciences at Kyoto University Graduate School of Medicine in Japan.
Sources of funding
Funding for this research was provided by: Diabetes Canada, Canadian Institutes of Health Research, National Sciences and Engineering Research Council of Canada, The Foundation Fighting Blindness Canada, the Fonds de Recherche en Ophtalmologie de l’Université de Montréal (FROUM), the Réseau en Recherche en Santé de la Vision, the Canadian Foundation for Innovation and the Montreal Heart Institute Foundation
