Past studies have shown that the immune system plays a role in obesity, but those studies were performed on mice deliberately fed a high-fat diet. The new Weizmann study, published recently in Immunity, was performed on mice fed a regular diet. It showed that immunological mechanisms can play a role in obesity and the other components of metabolic syndrome without connection to dietary fat.
The study originally focused on dendritic cells, which serve as the immune system’s sentinels, alerting other immune mechanisms to various dangers. The team’s emphasis was on a rare subtype of dendritic cells that possess a killing protein, called perforin, that enables them to eliminate other cells on demand. To reveal the function of these cells in the body, researchers – headed by Prof. Yair Reisner of the Department of Immunology – created mice that lacked perforin-rich dendritic cells. To the team’s surprise, the mice became overweight and then developed symptoms of metabolic syndrome.
Investigating these mice further, the researchers found that their fat tissue had abnormally high levels of inflammation-causing immune T cells. When these cells were removed from the fat tissue of the perforin-poor mice, the mice did not grow obese. These findings suggest that perforin-rich dendritic cells regulate the levels of certain T cells, and by keeping these T cells in check, they apparently prevent metabolic syndrome.
In addition to providing new insights into metabolic syndrome, the study may also shed new light on autoimmunity, as the mice lacking perforin-rich dendritic cells were more prone than usual to develop an autoimmune disease equivalent to multiple sclerosis in humans. It now remains to be investigated whether patients with autoimmune disease lack these regulatory cells.
The study was performed by members of Prof. Reisner’s team in collaboration with other Department of Immunology colleagues: Dr. Yael Zlotnikov-Klionsky, Bar Nathansohn-Levi, Dr. Elias Shezen, Dr. Chava Rosen, Dr. Sivan Kagan, Dr. Liat Bar-On, Prof. Steffen Jung, Dr. Eric Shifrut, Dr. Shlomit Reich-Zeliger, Dr. Nir Friedman, Dr. Rina Aharoni, Prof. Ruth Arnon, Oren Yifa, and Dr. Anna Aronovich.
Prof. Yair Reisner’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Steven and Beverly Rubenstein Charitable Foundation; and Roberto and Renata Ruhman, Brazil. Prof. Reisner is the incumbent of the Henry H. Drake Professorial Chair of Immunology.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. The Institute’s 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.
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