Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 47, Pages 23813-23821Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1912573116
Keywords
ketone body; fasting; low carbohydrate; gut microbiota; FFAR2
Categories
Funding
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology (KAKENHI) [JP15H05344, JP16H01355, JP18K19731, JP18K17920]
- Japan Agency for Medical Research and Development [JP17gm1010007]
- Lotte Foundation
- Institute for Fermentation Osaka
- Food Science Institute Foundation
- Smoking Research Foundation
- Uehara Memorial Foundation
Ask authors/readers for more resources
Ketone bodies, including beta-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. beta-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system. Under ketogenic conditions, such as starvation and low-carbohydrate diets, plasma acetoacetate levels increased markedly, whereas plasma and cecal SCFA levels decreased dramatically, along with an altered gut microbiota composition. In addition, Gpr43-deficient mice showed reduced weight loss and suppressed plasma lipoprotein lipase activity during fasting and eucaloric ketogenic diet feeding. Moreover, Gpr43-deficient mice exhibited minimal weight decrease after intermittent fasting. These observations provide insight into the role of ketone bodies in energy metabolism under shifts in nutrition and may contribute to the development of preventive medicine via diet and foods.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available