Metabolic Regulation via Gut Metabolites and Gastrointestinal Hormones

December 12, 2024

Toward unraveling the gut microbiota-hormone-brain system

The hormone vasopressin, secreted by the pituitary gland, regulates blood pressure, body fluid balance, emotional behavior, and social behavior. Mice lacking the vasopressin receptor exhibit abnormalities in glucose and lipid metabolism. A joint research group from the University of Tokyo, Tokyo Medical University, Iwate University, the RIKEN CSRS, the National Institute for Environmental Studies, and the National Center for Child Health and Development has uncovered the mechanism by which these metabolic abnormalities arise in these mice.

The team found excessive lipid accumulation in skeletal muscle and adipose tissue of vasopressin receptor-deficient mice, which is responsible for the breakdown of lipids to generate heat. Furthermore, they discovered a decrease in blood levels of the gut hormone glucagon-like peptide-1 (GLP-1). Since GLP-1 secretion is regulated by diet and metabolites produced by the gut microbiota, they examined the composition of the gut microbiota and its metabolites. Their analysis revealed an increase in butyrate-producing gut bacteria (Clostridium IV) and elevated butyrate levels. Notably, long-term culture of enteroendocrine L-cells, which secrete GLP-1, with butyrate resulted in reduced GLP-1 secretion capacity.

These findings are expected to contribute to the development of therapeutic strategies for various diseases, with a focus on the gut microbiota and its metabolites.

Original article

Molecular Metabolism doi: 10.1016/j.molmet.2024.102072

K. Harada, E. Wada, Y. Osuga, K. Shimizu, R. Uenoyama, M. Yokota Hirai, F. Maekawa, M. Miyazaki, Y. K. Hayashi, K. Nakamura, T. Tsuboi,

"Intestinal butyric acid-mediated disruption of gut hormone secretion and lipid metabolism in vasopressin receptor-deficient mice".

Contact

Masami Hirai
Team Leader
Metabolic Systems Research Team