{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:02:35Z","timestamp":1779706955614,"version":"3.53.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012317","name":"UCLH Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012891","name":"Medical Research Charities Group","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012891","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      We have previously shown that, in comparison with wild-type mice, mice that lack a functional flavin-containing monooxygenase 5 gene (\n                      <jats:italic>\n                        Fmo5\n                        <jats:sup>-\/-<\/jats:sup>\n                      <\/jats:italic>\n                      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\n                      <jats:italic>\n                        Fmo5\n                        <jats:sup>-\/-<\/jats:sup>\n                      <\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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                      <jats:italic>N<\/jats:italic>\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\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      ,\n                      <jats:italic>B. globosum<\/jats:italic>\n                      and\n                      <jats:italic>B. 388775<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1721571","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T10:08:36Z","timestamp":1779703716000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The 2R, 3R isomer of 2, 3-butanediol prevents weight gain and decreases plasma glucose concentration of mice fed a fat-enriched diet"],"prefix":"10.3389","volume":"17","author":[{"given":"Sunil","family":"Veeravalli","sequence":"first","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toryn M.","family":"Poolman","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy R.","family":"Everett","sequence":"additional","affiliation":[{"name":"Medway Metabonomics Research Group, University of Greenwich","place":["Chatham Maritime, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London","place":["London, United Kingdom"]},{"name":"School of Biological and Behavioural Sciences, Queen Mary University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Shephard","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1080\/13813455.2017.1398262","article-title":"The microbial metabolite indole-3-propionic acid improves glucose metabolism in rats, but does not affect behaviour","volume":"124","author":"Abildgaard","year":"2018","journal-title":"Arch. 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