"In their study, published in the February 16 online issue of Nature Medicine, the researchers described how the compound ß-hydroxybutyrate (BHB) directly inhibits NLRP3, which is part of a complex set of proteins called the inflammasome.
The inflammasome drives the inflammatory response in several disorders including autoimmune diseases, type 2 diabetes, Alzheimer’s disease, atherosclerosis, and autoinflammatory disorders.
“These findings are important because endogenous 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.
BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.
Dixit and colleagues focused on how macrophages — specialized immune cells that produce inflammation — respond when exposed to ketone bodies and whether that impacts the inflammasome complex.
The team introduced BHB to mouse models of inflammatorydiseases caused by NLP3. 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." SciTechDaily
“These findings are important because endogenous 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.
BHB is a metabolite produced by the body in response to fasting, high-intensity exercise, caloric restriction, or consumption of the low-carbohydrate ketogenic diet. Dixit said it is well known that fasting and calorie restriction reduces inflammation in the body, but it was unclear how immune cells adapt to reduced availability of glucose and if they can respond to metabolites produced from fat oxidation.
Dixit and colleagues focused on how macrophages — specialized immune cells that produce inflammation — respond when exposed to ketone bodies and whether that impacts the inflammasome complex.
The team introduced BHB to mouse models of inflammatorydiseases caused by NLP3. 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." SciTechDaily






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