{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:46:17Z","timestamp":1790063177717,"version":"4.0.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK105346"],"award-info":[{"award-number":["R01-DK105346"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P41-GM122698"],"award-info":[{"award-number":["P41-GM122698"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5U2C-DK119889"],"award-info":[{"award-number":["5U2C-DK119889"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The role of ketones in metabolic health has progressed over the past two decades, moving from what was perceived as a simple byproduct of fatty acid oxidation to a central player in a multiplicity of disease states. Previous work with hyperpolarized (HP) <jats:sup>13<\/jats:sup>C has shown that ketone production can be detected when using precursors that labeled acetyl-CoA at the C1 position, often in tissues that are not normally recognized as ketogenic. Here, we assay metabolism of HP [2-<jats:sup>13<\/jats:sup>C]pyruvate in the perfused mouse liver, a classic metabolic testbed where nutritional conditions can be precisely controlled. Livers perfused with long-chain fatty acids or the medium-chain fatty acid octanoate showed no evidence of ketogenesis in the <jats:sup>13<\/jats:sup>C spectrum. In contrast, addition of dichloroacetate, a potent inhibitor of pyruvate dehydrogenase kinase, resulted in significant production of both acetoacetate and 3-hydroxybutyrate from the pyruvate precursor. This result indicates that ketones are readily produced from carbohydrates, but only in the case where pyruvate dehydrogenase activity is upregulated.<\/jats:p>","DOI":"10.3389\/fphys.2022.832403","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T06:57:22Z","timestamp":1644217042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Detecting de novo Hepatic Ketogenesis Using Hyperpolarized [2-13C] Pyruvate"],"prefix":"10.3389","volume":"13","author":[{"given":"Mukundan","family":"Ragavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"McLeod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rushin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Merritt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"10158","DOI":"10.1073\/pnas.1733835100","article-title":"Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR","volume":"100","author":"Ardenkj\u00e6r-Larsen","year":"2003","journal-title":"PNAS"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/0026-0495(79)90166-5","article-title":"Kinetics of ketone body metabolism in fasting humans","volume":"28","author":"Balasse","year":"1979","journal-title":"Metabolism"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1002\/dmr.5610050304","article-title":"Ketone body production and disposal: effects of fasting, diabetes, and exercise","volume":"5","author":"Balasse","year":"1989","journal-title":"Diabetes Metab. 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