Anti-inflammatory mechanism of dieting and fasting revealed

Researchers at Yale School of Medicine have found that a compound 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.

In their study, published in the Feb. 16 online issue of Nature Medicine, the researchers described how the compound β-hydroxybutyrate (BHB) directly inhibits NLRP3, which is part of a complex set of proteins called the inflammasome. The inflammasome drives the 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 , 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, , 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.

Working with mice and , Dixit and colleagues focused on how macrophages—specialized immune cells that produce inflammation—respond when exposed to ketone bodies and whether that impacts the inflammasone complex.

The team introduced BHB to mouse models of inflammatory diseases caused by NLP3. They found that this reduced inflammation, and that inflammation was also reduced when the mice were given a , 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.


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More information: The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease, Nature Medicine, dx.doi.org/10.1038/nm.3804

Related paper: A small - molecule inhibitior of the NLRP3 inflammasome for the treatment of inflammatory diseases, Nature Medicine, dx.doi.org/10.1038/nm.3806

See: Team uncovers marvel molecule that could lead to treatments for inflammatory diseases

Journal information: Nature Medicine

Provided by Yale University
Citation: Anti-inflammatory mechanism of dieting and fasting revealed (2015, February 16) retrieved 26 May 2019 from https://medicalxpress.com/news/2015-02-anti-inflammatory-mechanism-dieting-fasting-revealed.html
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