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@article{Veeravalli:2022:10.3389/fphys.2022.859681,
author = {Veeravalli, S and Varshavi, D and Scott, FH and Varshavi, D and Pullen, FS and Veselkov, K and Phillips, IR and Everett, JR and Shephard, EA},
doi = {10.3389/fphys.2022.859681},
journal = {Frontiers in Physiology},
pages = {1--13},
title = {Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of Fmo5(-/-) mice, decreases plasma cholesterol and epididymal fat deposition},
url = {http://dx.doi.org/10.3389/fphys.2022.859681},
volume = {13},
year = {2022}
}

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TY  - JOUR
AB  - 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.
AU  - Veeravalli,S
AU  - Varshavi,D
AU  - Scott,FH
AU  - Varshavi,D
AU  - Pullen,FS
AU  - Veselkov,K
AU  - Phillips,IR
AU  - Everett,JR
AU  - Shephard,EA
DO  - 10.3389/fphys.2022.859681
EP  - 13
PY  - 2022///
SN  - 1664-042X
SP  - 1
TI  - Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of Fmo5(-/-) mice, decreases plasma cholesterol and epididymal fat deposition
T2  - Frontiers in Physiology
UR  - http://dx.doi.org/10.3389/fphys.2022.859681
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000843496600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.frontiersin.org/articles/10.3389/fphys.2022.859681/full
UR  - http://hdl.handle.net/10044/1/104410
VL  - 13
ER  -

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