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Published on: November 27, 2019
The 2R, 3R isomer of 2, 3-butanediol prevents weight gain and decreases plasma glucose concentration of mice fed a
Sunil Veeravalli1, Toryn M Poolman1, Jeremy R Everett2
1Department of Structural and Molecular Biology, University College London, London, United Kingdom.
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.
Insights
2R, 3R-butanediol effectively prevents weight gain and lowers plasma glucose in mice on a high-fat diet. This isomer also alters liver metabolites and gut microbiota, suggesting potential therapeutic use for weight management in humans.
Area of Science:
- Metabolic research
- Microbiome studies
- Biomarker discovery
Background:
- Flavin-containing monooxygenase 5 (Fmo5) gene knockout mice show reduced weight gain, fat deposition, and lower plasma cholesterol and glucose.
- Isomers of 2, 3-butanediol were identified as urinary biomarkers in Fmo5 knockout mice.
- Previous studies showed 2, 3-butanediol isomer mix reduced fat deposition and plasma cholesterol in wild-type mice.
Purpose of the Study:
- To investigate the effects of individual 2, 3-butanediol isomers on weight gain and plasma metabolites in mice fed a high-fat diet.
- To explore the impact of 2, 3-butanediol isomers on liver metabolites and gut microbiota composition.
Main Methods:
- Mice were fed either a standard chow or a 16% fat-enriched diet.
- Mice on the fat-enriched diet received no treatment or were treated with specific 2, 3-butanediol isomers (2R,3R; 2S,3S; meso) or a mixture.
- Analyses included body weight, plasma and liver metabolite concentrations, and gut microbiota composition.
Main Results:
- Treatment with 2R, 3R-butanediol prevented weight gain and decreased plasma glucose in mice on the fat-enriched diet.
- 2R, 3R-Butanediol increased liver concentrations of indolepropionate, N-delta-acetylornithine, and 1-myristoyl-2-arachidonoyl-glycerophosphorylcholine.
- Gut microbiota in 2R, 3R-butanediol treated mice showed depletion of Bacteroidota and enrichment of Actinomycetota, including Bifidobacterium species.
Conclusions:
- 2R, 3R-butanediol acts as an anti-obesogenic agent, preventing weight gain and reducing plasma glucose in mice on a high-fat diet.
- Potential mechanisms include increased liver indolepropionate and altered gut microbiota composition (enriched Bifidobacterium).
- Results suggest 2R, 3R-butanediol could be a therapeutic agent for suppressing weight gain in humans.
