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​Ketone bodies and receptors

​Reevaluation of ketone bodies

Ketone bodies have been discovered as substances for more than 100 years, but it is only in the last 20 years that we have begun to understand their physiological effects. During that time, countless papers have been published among researchers, and the various effects of ketone bodies have been highly evaluated. Two of them are particularly interesting here. First, unlike other organic acids, ketone bodies have specific receptors on the cell membrane. The two main proposed receptors for ketone bodies are:
 
HCR2
(H car two)
With the discovery of HCAR2, ketone bodies have come to be recognized as molecules with special physiological effects that differ from other organic acids. HCAR2 can be activated by organic acids with hydroxyl groups, but it is particularly strongly activated by ketone bodies, and is involved in many physiological activities such as anti-inflammatory action and lipolysis.

​​GPR43
(GP 43)
The most prominent physiological effect caused by an increase in ketone bodies is the decomposition of fat.
Many researchers thought that there might be a special receptor for this, but last year (September 2019) it was discovered that it was a protein called GPR43. When carbohydrates are restricted, the concentration of ketone bodies increases and GPR43 is activated, so fat is preferentially broken down.
 

(*References 1​Graff EC, Fang H, Wanders D, Judd RL. Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2. Metabolism. 2016 Feb;65(2):102-13. doi: 10.1016/j.metabol.2015.10.001. Epub 2015 Nov 13. PMID: 26773933.

(*References 2Miyamoto J, Ohue-Kitano R, Mukouyama H, Nishida A, Watanabe K, Igarashi M, Irie J, Tsujimoto G, Satoh-Asahara N, Itoh H, Kimura I. Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions. Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23813-23821. doi: 10.1073/pnas.1912573116. Epub 2019 Nov 4. PMID: 31685604;

HP用受容体 トリミング.png

When ketone bodies bind to receptor proteins such as HCAR2 in immune cells and GPR43 in adipocytes, they amplify signals within immune cells and adipocytes. ​The paper suggests that by amplifying intracellular signals, it suppresses inflammatory responses and inhibits fat synthesis.

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