A research group led by Professor Ikuo Kimura of Tokyo University of Agriculture and Technology has found that acetoacetic acid, a type of ketone body, its receptors, and the intestinal environment have been shown to effectively reduce body fat weight by low-carbohydrate diets and intermittent fasting. It was clarified that the change of was closely related.
Ketone bodies (mainly β-hydroxybutyric acid and acetoacetic acid) are important alternative energy sources produced by the liver during glucose depletion such as starvation. β-Hydroxybutyric acid is known to be involved in biophysiological function as a signal molecule via GPR109A and GPR41, which are receptors on the cell membrane (G protein-coupled receptor), but it is a specific receptor for acetoacetic acid. Has not been discovered.In addition, ketogenic diets that induce ketone body production, such as low-carbohydrate diets and medium-chain fatty acid diets, and intermittent fasting are expected to extend lifespan, effectively reduce weight, and improve brain function. There were many unclear points about the mechanism.
The research group has now discovered that the receptor for acetoacetic acid is GPR43 (one of the G protein-coupled receptors) by a method called "monocarboxylic acid ligand screening".Furthermore, in conditions such as fasting, low-carbohydrate diet and intermittent fasting (in a ketogenic environment), changes in the intestinal flora reduce short-chain fatty acids in the intestinal tract and suppress GPR43, but acetoacetic acid is suppressed systemically. It was clarified that GPR43 stimulation by GPRXNUMX enhances the activity of lipoprotein lipase (lipolytic enzyme) in blood, promotes the decomposition of triglyceride, and efficiently takes up fatty acids into tissues, resulting in increased utilization of lipids. ..
The results of this research are expected to contribute to the development of preemptive medicine and preventive medicine through dietary intervention and nutritional management, as well as therapeutic agents for metabolic diseases targeting ketone body receptors.
Paper information:[Proceedings of the American Academy of Sciences (PNAS)] Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions
