Veeravalli, Sunil;
Dorsa, Varshavi;
Scott, Flora;
Dorna, Varshavi;
Pullen, Frank;
Kirill, Veselkov;
Phillips, Ian;
... Shephard, Elizabeth; + view all
(2022)
Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of fmo5-/- mice, decreases plasma cholesterol and epididymal fat deposition.
Frontiers in Physiology
, 13
, Article 859681. 10.3389/fphys.2022.859681.
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Abstract
We previously showed that Fmo5−/− mice exhibit a lean phenotype and slower metabolic ageing. Their characteristics include lower plasma glucose and cholesterol, greater glucose tolerance and insulin sensitivity, and a reduction in age-related weight gain and whole-body fat deposition. In this paper, nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of the urine of Fmo5−/− and wild-type mice identified two isomers of 2,3-butanediol as discriminating urinary biomarkers of Fmo5−/− mice. Antibiotic-treatment of Fmo5−/− mice increased plasma cholesterol concentration and substantially reduced urinary excretion of 2,3-butanediol isomers, indicating that the gut microbiome contributed to the lower plasma cholesterol of Fmo5−/− mice, and that 2,3-butanediol is microbially derived. Short- and long-term treatment of wild-type mice with a 2,3-butanediol isomer mix decreased plasma cholesterol and epididymal fat deposition but had no effect on plasma concentrations of glucose or insulin, or on body weight. In the case of long-term treatment, the effects were maintained after withdrawal of 2,3-butanediol. Short-, but not long-term treatment, also decreased plasma concentrations of triglycerides and non-esterified fatty acids. Fecal transplant from Fmo5−/− to wild-type mice had no effect on plasma cholesterol, and 2,3-butanediol was not detected in the urine of recipient mice, suggesting that the microbiota of the large intestine was not the source of 2,3-butanediol. However, 2,3-butanediol was detected in the stomach of Fmo5−/− mice, which was enriched for Lactobacillus genera, known to produce 2,3-butanediol. Our results indicate a microbial contribution to the phenotypic characteristic of Fmo5−/− mice of decreased plasma cholesterol and identify 2,3-butanediol as a potential agent for lowering plasma cholesterol.
| Type: | Article |
|---|---|
| Title: | Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of fmo5-/- mice, decreases plasma cholesterol and epididymal fat deposition |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fphys.2022.859681 |
| Publisher version: | https://doi.org/10.3389/fphys.2022.859681 |
| Language: | English |
| Additional information: | Copyright © 2022 Veeravalli, Varshavi, Scott, Varshavi, Pullen, Veselkov, Phillips, Everett and Shephard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | antibiotic, fecal transplant, gut microbiome, metabolite, NMR, stomach, urine, cholesterol |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10154286 |
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