In a groundbreaking discovery, a research team led by University Professor Daniel Drucker at Sinai Health’s Lunenfeld-Tanenbaum Research Institute and the University of Toronto’s Temerty Faculty of Medicine has identified a gut-brain-immune network that plays a crucial role in controlling inflammation throughout the body, impacting organ health. The findings, published in Cell Metabolism, shed light on the mechanisms behind the anti-inflammatory effects of glucagon-like peptide-1 (GLP-1) receptor agonists.
GLP-1 receptor agonists are commonly used by clinicians to treat Type 2 diabetes, demonstrating effectiveness in not only managing blood sugar levels but also promoting weight loss. The recent study delves into the additional benefits of these drugs, revealing their ability to reduce complications associated with chronic metabolic diseases.
While clinical studies have shown the positive impact of GLP-1 drugs, the exact mechanisms underlying their effects were not fully understood. The research team, led by Dr. Daniel Drucker, aimed to uncover the mystery by investigating how GLP-1 drugs alleviate inflammation, a common issue in chronic metabolic diseases.
Contrary to previous assumptions that GLP-1 receptors on immune cells are solely responsible for dampening inflammation, the team discovered a more complex gut-brain-immune axis. While GLP-1 receptors are abundant in the gut, other organs lack a significant number of these receptors. This led the researchers to explore the role of the brain, where GLP-1 receptors are plentiful and where communication with the immune system and other organs occurs.
The team, led by Chi Kin Wong, induced systemic inflammation in mice and observed that GLP-1 agonists effectively reduced inflammation, but only when their receptors in the brain were unblocked. When these brain receptors were inhibited, the drugs’ ability to reduce inflammation was lost. This groundbreaking discovery points to the existence of a GLP-1-brain-immune axis controlling inflammation across the body, even in organs lacking GLP-1 receptors.
Dr. Daniel Drucker, renowned for his contributions to GLP-1 research, has previously received prestigious awards, including the 2023 VinFuture Emerging Innovation Prize and the 2023 Wolf Prize in Medicine. GLP-1-based diabetes drugs arising from his earlier research were named the 2023 Breakthrough of the Year by the journal Science.
Anne-Claude Gingras, director of the Lunenfeld-Tanenbaum Research Institute, expressed admiration for Drucker’s tenacity in unraveling the complexities of GLP-1 drugs. The ongoing research aims to identify specific brain cells interacting with GLP-1 and explore various mouse models of inflammation, such as heart disease, atherosclerosis, and liver and kidney inflammation.
Drucker believes that understanding how GLP-1 dampens inflammation may pave the way for new strategies to reduce complications associated with Type 2 diabetes and obesity. The study, funded by the Canadian Institutes for Health Research and Novo Nordisk Inc., signifies a significant step forward in the scientific community’s understanding of the expanding clinical impact of GLP-1.
