Veeravalli, Sunil, Poolman, Toryn M., Everett, Jeremy R., Phillips, Ian R. and Shephard, Elizabeth A. (2026) The 2R,3R isomer of 2,3-butanediol prevents weight gain and decreases plasma glucose concentration of mice fed a fat-enriched diet. Frontiers in Physiology, 17:1721571. ISSN 1664-042X (Online) (doi:10.3389/fphys.2026.1721571)

Preview

PDF (Open Access Article) 53469 EVERETT_The_2R_3R_Isomer_of_2_3_Butanediol_Prevents_Weight_Gain_(OA)_2026.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

Abstract

Background: We have previously shown that, in comparison with wild-type mice, mice that lack a functional flavin-containing monooxygenase 5 gene (Fmo5-/- mice) exhibit reduced weight gain as they age, reduced fat deposition, and lower plasma concentrations of total cholesterol and glucose. We also identified isomers of 2,3-butanediol as urinary biomarkers of Fmo5-/- mice. Treatment of male, wild-type mice fed a standard chow diet, with a 2,3-butanediol isomer mix resulted in reduced epidydimal fat deposition and lower plasma cholesterol concentration. In the current study we explored the influence of individual isomers of 2,3-butanediol on weight gain and plasma metabolite concentrations of wild-type mice fed a fat-enriched diet. We also investigated the effect of 2,3-butanediol isomers on liver metabolites and gut microbiota.

Methods: Mice were fed a standard chow or a 16% fat-enriched diet. Mice on the fat-enriched diet were untreated or treated with 2R,3R-butanediol, 2S,3S-butanediol, meso-2,3-butanediol or a mix of the three isomers. Mice were analyzed for weight, plasma and liver metabolite concentrations and gut microbiota composition.

Results: Treatment with 2R,3R-butanediol prevented weight gain and decreased plasma glucose concentration of mice fed the fat-enriched diet. 2R,3R-Butanediol increased the concentrations of three of the 693 liver metabolites identified: indolepropionate, N-delta-acetylornithine and 1-myristoyl-2-arachidonoyl-glycerophosphorylcholine (14:0/20:4). In comparison with untreated mice fed the fat-enriched diet, the gut microbiota of mice treated with 2R,3R-butanediol was depleted in the Bacteroidota (Bacteroidetes) phylum and enriched in the Actinomycetota phylum, particularly in two species of Bifidobacterium, B. globosum and B. 388775.

Conclusions: We have identified 2R,3R-butanediol as an effective anti-obesogenic agent that prevents weight gain and decreases plasma glucose of mice fed a fat-enriched diet. The effect of 2R,3R-butanediol may be due, in part, to its ability to increase the concentration of indolepropionate in the liver and of the proportion of Bifidobacterium species in the gut microbiota, both of which are known to have beneficial effects on weight control and plasma glucose concentration. Our results suggest that 2R,3R-butanediol may be of value as a therapeutic agent to suppress weight gain in humans.

Item Type:	Article
Additional Information:	The author(s) declared that financial support was received for this work and/or its publication. This work was supported by funds provided by UCL Therapeutic Acceleration Support scheme sup ported by funding from UCL’s MRC Confidence in Concept 2016 MC/PC/16063 and NIHR UCLH Biomedical Research Centre BRC423/JK/101400 awards.
Uncontrolled Keywords:	anti-obesogen, Bifidobacterium, flavin-containing monooxygenase, FMO5, gut microbiota, indolepropionate, liver metabolites
Subjects:	Q Science > Q Science (General) Q Science > QP Physiology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Related URLs:	Publisher
Last Modified:	27 May 2026 08:54
URI:	https://gala.gre.ac.uk/id/eprint/53469

Actions (login required)

View Item

Downloads