A Tougher Defense Against Dangerous Inflammation

By Jane Farrell

A compound that’s produced by the body when dieting or fasting can block a part of the immune system involved in several inflammatory disorders such as type 2 diabetes, atherosclerosis, and Alzheimer’s disease, according to a study from the Yale School of Medicine.

The study, published in the journal Nature Medicine, focuses on how the compound β-hydroxybutyrate (BHB) directly inhibits NLRP3, which is part of a complex set of proteins called the inflammasome. According to a news release from the Yale medical school, the inflammasome drives the inflammatory response in several disorders including autoimmune diseases, type 2 diabetes, Alzheimer’s disease, atherosclerosis, and autoinflammatory disorders.

BHB is produced by the body in response to fasting, high-intensity exercise, restricted calorie intake or following the low-carbohydrate ketogenic diet. The investigators worked with mice and human immune cells, focusing on how macrophages —immune cells that produce inflammation — respond when exposed to “ketone bodies” and whether that impacts the inflammasone complex.

“These findings are important because…metabolites like BHB that block the NLRP3 inflammasome could be relevant against many inflammatory diseases, including those where there are mutations in the NLRP3 genes,” said Vishwa Deep Dixit, professor in the Section of Comparative Medicine at Yale School of Medicine.

The team introduced BHB to mouse models of inflammatory diseases caused by NLRP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a ketogenic diet, which elevates the levels of BHB in the bloodstream.

“Our results suggest that the endogenous metabolites like BHB that are produced during low-carb dieting, fasting, or high-intensity exercise can lower the NLRP3 inflammasome,” said Dixit.