Reutericyclin mitigates risperidone-induced suppression of anaerobic energy expenditure. Am J Physiol Regul Integr Comp Physiol 2025 Jun 01;328(6):R741-R757
Date
04/16/2025Pubmed ID
40235074Pubmed Central ID
PMC12128854DOI
10.1152/ajpregu.00190.2024Scopus ID
2-s2.0-105006676606 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Recent studies from our laboratory demonstrated that the gut microbial community represents a thermogenic biomass, as cecectomy causes an ∼8% decrease in total energy expenditure (EE) via suppression of anaerobic EE. The composition of the microbial community also dictates the EE of the microbial biomass as treatment with the antipsychotic, risperidone, suppresses anaerobic EE in a microbiome-dependent manner. Finally, we have determined that a specialized metabolite produced by Limosilactobacillus reuteri, reutericyclin (RTC), opposes the weight-gain effects of risperidone. In the present study, we performed comprehensive evaluations of energy balance in female C57BL/6J mice treated with risperidone, RTC, or both, to identify mechanisms by which RTC affects energy balance to mitigate risperidone-induced weight gain. We observed that risperidone suppressed anaerobic EE, and that RTC coadministration ameliorated the anaerobic EE suppression and weight gain induced by risperidone. Because anaerobic EE is dependent on the gut microbiota, we performed 16S and whole genome shotgun sequencing on stool and cecal samples following whole animal calorimetry. Risperidone and RTC treatments reciprocally modified the relative abundance of taxa known to participate in fermentation, especially for the production of short-chain fatty acids, which have been correlated with health and leanness in both humans and mice. Together, our data demonstrate that treatment with RTC positively modulates anaerobic EE, possibly by enhancing fermentation of the gut microbial community, and may represent a novel therapeutic in the treatment of obesity.NEW & NOTEWORTHY The gut microbial community represents a thermogenic biomass. The composition of the microbial community dictates energy expenditure of the microbial biomass and is altered by xenobiotics and bacterial metabolites. This study demonstrates that treatment with reutericyclin positively modulates anaerobic energy expenditure and may represent a novel therapeutic in the treatment of obesity.
Author List
Hadiono MA, Kazen AB, Aboulalazm FA, Burnett CML, Reho JJ, Kindel TL, Grobe JL, Kirby JRAuthors
Colin M. Burnett MD Assistant Professor in the Medicine department at Medical College of WisconsinJustin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Tammy Lyn Kindel PhD, MD Professor in the Surgery department at Medical College of Wisconsin
John Kirby PhD Chair, Center Associate Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnaerobiosisAnimals
Antipsychotic Agents
Energy Metabolism
Female
Gastrointestinal Microbiome
Mice
Mice, Inbred C57BL
Risperidone
Weight Gain
